日本血吸虫虫源抗原与抗原递呈细胞的相互作用的（体外）实验研究
|
摘要
日本血吸虫病(schistosomiasis japonica)迄今仍然是我国主要公共卫生问题之一。依据疾病传播的生态学原理确定的综合防治措施虽然有效,但效果难以巩固。鉴于疫苗在许多传染病控制中无可比拟的作用,试图发展血吸虫病疫苗是二十世纪六十年代以来世界各国有关科学家为之奋斗的目标。但经过长期努力,迄今尚未能成功研制出有效的抗血吸虫感染的疫苗,其原因在于对血吸虫感染中存在的一些免疫现象及其分子机制的认识还比较模糊,因而极大地限制了我们明确选择日本血吸虫病疫苗发展。
辐照致弱尾蚴疫苗免疫可以诱导相对高水平的保护力。由于现实的条件和伦理的原因,不能以辐照致弱尾蚴直接免疫人。关于辐照尾蚴免疫诱导高保护力的机制,现有的主要观点是:辐照诱导了尾蚴成分的改变并因此更加有效地诱导了免疫活化;另一种观点认为辐照致弱尾蚴不能发育为成虫产卵,从而避免了虫卵沉积和虫卵抗原释放对宿主免疫应答的下调和抑制作用,从而可以使机体内存在的,已经被辐照致弱尾蚴抗原(attenuated cercaria antigen, ACA)活化的免疫细胞,对再次接触到的来自正常尾蚴的抗原发生有效的活化并发挥有效的攻击和杀伤效应。以往研究多以体内实验对获得性免疫应答的免疫效应进行观察和分析,或者对正常尾蚴抗原(normal cercaria antigen, NCA)与ACA组分进行比较分析。这些研究结果为理解辐照致弱尾蚴诱导保护力的分子机制提供了诸多支持。
基于先天免疫在启动和调节免疫应答中的重要作用,观察和比较日本血吸虫NCA和/或ACA以及可溶性虫卵抗原(soluble egg antigen, SEA)对抗原递呈细胞(antigen presenting cells, APCs)的作用也具有重要意义,可为解释辐照致弱尾蚴诱导保护力的分子机制提供新的视角。一方面,APCs摄取病原体成分并降解为小分子抗原肽,通过主要组织相容性复合体Ⅱ类分子(major histocompatibility complexⅡ, MHCⅡ)递呈给T细胞受体(T cell receptor, TCR)识别;另一方面,APCs通过模式识别受体(pattern recognition receptors, PRRs)识别病原体相关的分子模式(pathogen-associated molecular pattern,.PAMP),启动信号转导和基因表达,分泌各种细胞因子对免疫应答起重要的调节作用。本研究基于APCs在启动和调节免疫应答中的关键作用,着眼于血吸虫抗原对MHCⅡ表达的调节,着重观察了血吸虫感染早期和晚期阶段涉及的两种重要抗原,即NCA、ACA和SEA对小鼠巨噬细胞模型细胞系RAW264.7的免疫调节。
本研究结果证实,日本血吸虫SEA可以显著抑制IFN-γ诱导的巨噬细胞MHCⅡ的表达;IFN-γ可以促进SEA诱导巨噬细胞分泌IL-10和IL-6;IL-10对介导SEA诱导的MHCⅡ下调起重要作用,SEA也通过诱导IL-6抑制MHCⅡ表达;在IFN-γ存在条件下,SEA诱导巨噬细胞分泌TGF-β的过程受到抑制并且未显示TGF-β对MHCⅡ的抑制作用; SEA通过TLR4识别下调巨噬细胞MHCⅡ表达。
本研究结果显示,NCA与ACA不同地调节巨噬细胞MHCⅡ分子表达,NCA可以显著下调IFN-γ诱导巨噬细胞表达MHCⅡ,而ACA对IFN-γ诱导巨噬细胞表达MHCⅡ不具有明显影响;NCA在IFN-γ存在条件下诱导巨噬细胞产生的IL-10、IL-6和PGE2均显著高于ACA刺激组。这些结果提示正常尾蚴可能通过诱导APCs分泌抑制性因子下调MHCⅡ表达实现免疫逃避,而辐照则可能由于导致尾蚴成分变化而废除或者抑制了其中抑制MHCⅡ表达的因素,从而有效地致敏和活化了T细胞。
总之,本研究从日本血吸虫尾蚴和虫卵抗原对MHCⅡ表达的调节的角度,为血吸虫感染后期免疫应答的下调和抑制以及正常尾蚴感染与辐照尾蚴免疫诱导的免疫应答活化和效应的差异提供了合理的解释,其中的相关分子机制值得进一步探讨。
Nowdays, schistosomiasis japonica is still one of the main public health problems in our country. Although the comprehensive measures based on the principle of disease transmission ecology were valid, the effectiveness is difficult to be consolidated. Based on the incomparable virtue of vaccine in controlling of many infectious diseases, anti-schistosomiasis vaccine development has been the objective of scientists in the world for past half century. Even with long-term endeavor, there is no effective anti-schistosome infection vaccine so far. Currently, some of the immunological phenomena and the related molecular mechanisms of Schistosoma japonicum infection are still unclear,which greatly limited our ability to choose the better tactic and approaches for developing anti-schistosomiasis vaccines.
Attenuated schistosome cercaria vaccine could induce relatively higher level of protection. But due to actual condition and ethics, attenuated cercariae vaccine can’t be used directly on humans. Many speculations and explanations for the mechanisms of protection induced by attenuated cercaria focuses on two aspects: Attenuation lead to the change of cercaria components and consequently will more effectively activate the immunocytes. Another opinion is that attenuated cercariae failed to mature into worms to lay eggs and therefore avoid the downregulation and suppression on host’s immune responses brought by eggs deposition and soluble egg antigen releasing, which will facilitate the effective activation of attenuated cercaria antigen-primed lymphocytes when the host’s lymphoctyes encount with normal cercariae again. Previous research mainly focused on in vivo observation and analysis of effective stage of acquired immune response or comparing normal and attenuated cercaria antigen components. These results have provided supports for understanding the molecular mechanisms of protection induced by attenuated cercariae.
Based on the important role of innate immunity playing in in immune initiation and regulation, to observe and compare the effect of normal and ultraviolet-attenuated cercaria antigen on antigen presenting cells (APCs) would also have important significance, which may supply new opinion for explaining the molecular mechanism of protection induced by radiation-attenuated cercariae. In one side, APCs uptake pathogen components and degrade them into small antigen peptides,which were presented by major histocompatibility complex II (MHC II) for being recognized by T cell receptor (TCR). On the other side, APCs recognize pathogen-associated molecular pattern (PAMP) through pattern recognition receptors (PRRs) and initiate signal transduction and gene expression, and secrete multiple cytokines playing important regulatory role on immune responses.
This research based on the key role of APCs in initiating and regulating immune responses, focused on of MHC II expression regulation. We mainly observed the immunoregulation of two types of important antigens involving in schistosome infection on early and late stage, that is, cercaria (normal cercaria antigen, NCA; and attenuated cercaria antigen, ACA) and egg antigens, on mouse macrophages model cell line RAW 264.7. Our research showed that Schistosoma japonicum soluble egg antigen (SEA) could significantly attenuate IFN-γ-induced MHC II expression on macrophages; IFN-γcould promote SEA-induced IL-10 and IL-6 production from macrophages; IL-10 played an important role in mediating SEA-induced MHC II suppression, SEA attenuated MHC II expression also through inducing IL-6 production; In presence of IFN-γ, TGF-βproduction induced by SEA from macrophages was suppressed, and thus at least in vitro, TGF-βwas irresponsible for the suppression of MHC II expression due to SEA.
Our results also demonstrated that NCA and ACA regulated MHC II expression on macrophages differently. That was, NCA could significantly attenuate IFN-γ-induced MHC II expression, but ACA showed nearly no impact on IFN-γ-induced MHC II expression in macrophages. Compared with ACA, NCA induced significantly increased IL-10, IL-6 and PGE2 production from macrophages in presence of IFN-γ. These results suggested that normal cercariae might evade immune attack through induction of suppressive cytokines to down-regulate MHC II expression. Ultraviolation might result in the change of cercaria components and abrogate or suppress the factors among them that can suppress MHC II expression and thus effectively prime and activate T lymphocytes.
In conclusion, this study explored the explanation for immune downregulation and suppression of during the late stage of schistosomiasis, as well as the discrepant immune responses induced by normal cercaria infection and attenuated cercaria vaccination. The underlying molecular mechanisms related with these findings merit further study.
辐照致弱尾蚴疫苗免疫可以诱导相对高水平的保护力。由于现实的条件和伦理的原因,不能以辐照致弱尾蚴直接免疫人。关于辐照尾蚴免疫诱导高保护力的机制,现有的主要观点是:辐照诱导了尾蚴成分的改变并因此更加有效地诱导了免疫活化;另一种观点认为辐照致弱尾蚴不能发育为成虫产卵,从而避免了虫卵沉积和虫卵抗原释放对宿主免疫应答的下调和抑制作用,从而可以使机体内存在的,已经被辐照致弱尾蚴抗原(attenuated cercaria antigen, ACA)活化的免疫细胞,对再次接触到的来自正常尾蚴的抗原发生有效的活化并发挥有效的攻击和杀伤效应。以往研究多以体内实验对获得性免疫应答的免疫效应进行观察和分析,或者对正常尾蚴抗原(normal cercaria antigen, NCA)与ACA组分进行比较分析。这些研究结果为理解辐照致弱尾蚴诱导保护力的分子机制提供了诸多支持。
基于先天免疫在启动和调节免疫应答中的重要作用,观察和比较日本血吸虫NCA和/或ACA以及可溶性虫卵抗原(soluble egg antigen, SEA)对抗原递呈细胞(antigen presenting cells, APCs)的作用也具有重要意义,可为解释辐照致弱尾蚴诱导保护力的分子机制提供新的视角。一方面,APCs摄取病原体成分并降解为小分子抗原肽,通过主要组织相容性复合体Ⅱ类分子(major histocompatibility complexⅡ, MHCⅡ)递呈给T细胞受体(T cell receptor, TCR)识别;另一方面,APCs通过模式识别受体(pattern recognition receptors, PRRs)识别病原体相关的分子模式(pathogen-associated molecular pattern,.PAMP),启动信号转导和基因表达,分泌各种细胞因子对免疫应答起重要的调节作用。本研究基于APCs在启动和调节免疫应答中的关键作用,着眼于血吸虫抗原对MHCⅡ表达的调节,着重观察了血吸虫感染早期和晚期阶段涉及的两种重要抗原,即NCA、ACA和SEA对小鼠巨噬细胞模型细胞系RAW264.7的免疫调节。
本研究结果证实,日本血吸虫SEA可以显著抑制IFN-γ诱导的巨噬细胞MHCⅡ的表达;IFN-γ可以促进SEA诱导巨噬细胞分泌IL-10和IL-6;IL-10对介导SEA诱导的MHCⅡ下调起重要作用,SEA也通过诱导IL-6抑制MHCⅡ表达;在IFN-γ存在条件下,SEA诱导巨噬细胞分泌TGF-β的过程受到抑制并且未显示TGF-β对MHCⅡ的抑制作用; SEA通过TLR4识别下调巨噬细胞MHCⅡ表达。
本研究结果显示,NCA与ACA不同地调节巨噬细胞MHCⅡ分子表达,NCA可以显著下调IFN-γ诱导巨噬细胞表达MHCⅡ,而ACA对IFN-γ诱导巨噬细胞表达MHCⅡ不具有明显影响;NCA在IFN-γ存在条件下诱导巨噬细胞产生的IL-10、IL-6和PGE2均显著高于ACA刺激组。这些结果提示正常尾蚴可能通过诱导APCs分泌抑制性因子下调MHCⅡ表达实现免疫逃避,而辐照则可能由于导致尾蚴成分变化而废除或者抑制了其中抑制MHCⅡ表达的因素,从而有效地致敏和活化了T细胞。
总之,本研究从日本血吸虫尾蚴和虫卵抗原对MHCⅡ表达的调节的角度,为血吸虫感染后期免疫应答的下调和抑制以及正常尾蚴感染与辐照尾蚴免疫诱导的免疫应答活化和效应的差异提供了合理的解释,其中的相关分子机制值得进一步探讨。
Nowdays, schistosomiasis japonica is still one of the main public health problems in our country. Although the comprehensive measures based on the principle of disease transmission ecology were valid, the effectiveness is difficult to be consolidated. Based on the incomparable virtue of vaccine in controlling of many infectious diseases, anti-schistosomiasis vaccine development has been the objective of scientists in the world for past half century. Even with long-term endeavor, there is no effective anti-schistosome infection vaccine so far. Currently, some of the immunological phenomena and the related molecular mechanisms of Schistosoma japonicum infection are still unclear,which greatly limited our ability to choose the better tactic and approaches for developing anti-schistosomiasis vaccines.
Attenuated schistosome cercaria vaccine could induce relatively higher level of protection. But due to actual condition and ethics, attenuated cercariae vaccine can’t be used directly on humans. Many speculations and explanations for the mechanisms of protection induced by attenuated cercaria focuses on two aspects: Attenuation lead to the change of cercaria components and consequently will more effectively activate the immunocytes. Another opinion is that attenuated cercariae failed to mature into worms to lay eggs and therefore avoid the downregulation and suppression on host’s immune responses brought by eggs deposition and soluble egg antigen releasing, which will facilitate the effective activation of attenuated cercaria antigen-primed lymphocytes when the host’s lymphoctyes encount with normal cercariae again. Previous research mainly focused on in vivo observation and analysis of effective stage of acquired immune response or comparing normal and attenuated cercaria antigen components. These results have provided supports for understanding the molecular mechanisms of protection induced by attenuated cercariae.
Based on the important role of innate immunity playing in in immune initiation and regulation, to observe and compare the effect of normal and ultraviolet-attenuated cercaria antigen on antigen presenting cells (APCs) would also have important significance, which may supply new opinion for explaining the molecular mechanism of protection induced by radiation-attenuated cercariae. In one side, APCs uptake pathogen components and degrade them into small antigen peptides,which were presented by major histocompatibility complex II (MHC II) for being recognized by T cell receptor (TCR). On the other side, APCs recognize pathogen-associated molecular pattern (PAMP) through pattern recognition receptors (PRRs) and initiate signal transduction and gene expression, and secrete multiple cytokines playing important regulatory role on immune responses.
This research based on the key role of APCs in initiating and regulating immune responses, focused on of MHC II expression regulation. We mainly observed the immunoregulation of two types of important antigens involving in schistosome infection on early and late stage, that is, cercaria (normal cercaria antigen, NCA; and attenuated cercaria antigen, ACA) and egg antigens, on mouse macrophages model cell line RAW 264.7. Our research showed that Schistosoma japonicum soluble egg antigen (SEA) could significantly attenuate IFN-γ-induced MHC II expression on macrophages; IFN-γcould promote SEA-induced IL-10 and IL-6 production from macrophages; IL-10 played an important role in mediating SEA-induced MHC II suppression, SEA attenuated MHC II expression also through inducing IL-6 production; In presence of IFN-γ, TGF-βproduction induced by SEA from macrophages was suppressed, and thus at least in vitro, TGF-βwas irresponsible for the suppression of MHC II expression due to SEA.
Our results also demonstrated that NCA and ACA regulated MHC II expression on macrophages differently. That was, NCA could significantly attenuate IFN-γ-induced MHC II expression, but ACA showed nearly no impact on IFN-γ-induced MHC II expression in macrophages. Compared with ACA, NCA induced significantly increased IL-10, IL-6 and PGE2 production from macrophages in presence of IFN-γ. These results suggested that normal cercariae might evade immune attack through induction of suppressive cytokines to down-regulate MHC II expression. Ultraviolation might result in the change of cercaria components and abrogate or suppress the factors among them that can suppress MHC II expression and thus effectively prime and activate T lymphocytes.
In conclusion, this study explored the explanation for immune downregulation and suppression of during the late stage of schistosomiasis, as well as the discrepant immune responses induced by normal cercaria infection and attenuated cercaria vaccination. The underlying molecular mechanisms related with these findings merit further study.
引文
1. EJ Pearce and AS MacDonald. The immunobiology of schistosomiasis. Nat Rev Immunol, 2002. 2(7): 499-511.
2. MJ Ji, C Su, et al. Gene expression profile of CD4+ T cells reveals an interferon signaling suppression associated with progression of experimental Schistosoma japonicum infection. Cell Immunol, 2003. 224(1): 55-62.
3. MJ Ji, C Su, et al. Characterization of CD4~+ T Cell Responses in Mice Infected with Schistosoma japonicum. Acta Biochim Biophys Sin, 2006. 38: 327 - 334.
4. RA Wilson and PS Coulson. Why don't we have a schistosomiasis vaccine? Parasitol Today, 1998. 14(3): 97-9.
5. RA Wilson, PS Coulson, et al. Immune responses to the radiation-attenuated schistosome vaccine: what can we learn from knock-out mice? Immunol Lett, 1999. 65(1-2): 117-23.
6. DA Vignali, P Crocker, et al. A role for CD4+ but not CD8+ T cells in immunity to Schistosoma mansoni induced by 20 krad-irradiated and Ro 11-3128-terminated infections. Immunology, 1989. 67(4): 466-72.
7. LE Smythies, RM Pemberton, et al. T cell-derived cytokines associated with pulmonary immune mechanisms in mice vaccinated with irradiated cercariae of Schistosoma mansoni. J. Immunol., 1992. 148: 1512-1518.
8. S Anderson, VL Shires, et al. In the absence of IL-12, the induction of Th1-mediated protective immunity by the attenuated schistosome vaccine is impaired, revealing an alternative pathway with Th2-type characteristics. Eur J Immunol, 1998. 28(9): 2827-38.
9. S Anderson, PS Coulson, et al. The radiation-attenuated schistosome vaccine induces high levels of protective immunity in the absence of B cells. Immunology, 1999. 96(1): 22-8.
10. EC Ratcliffe and RA Wilson. The role of mononuclear-cell recruitment to the lungs in the development and expression of immunity to Schistosoma mansoni. Parasitology, 1992. 104: 299-307.
11. JE Crabtree and RA Wilson. The role of pulmonary cellular reactions in the resistance of vaccinated mice to Schistosoma mansoni. Parasite Immunol, 1986. 8(3): 265-85.
12. RA Wilson, PS Coulson, et al. Impaired immunity and altered pulmonary responses in mice with a disrupted interferon-γreceptor gene exposed to the irradiated Schistosoma mansoni vaccine. Immunology, 1996. 87(2): 275-82.
13. Z Caulada-Benedetti, F al-Zamel, et al. Comparison of Th1- and Th2-associated immune reactivities stimulated by single versus multiple vaccination of mice with irradiated Schistosoma mansoni cercariae. J. Immunol., 1991. 146: 1655 - 1660.
14. KS Warren, EO Domingo, et al. Granuloma formation around schistosome eggs as a manifestation of delayed hypersensitivity. Am. J. Pathol., 1967. 51: 735 - 756.
15. RD Buchanan, DP Fine, et al. Schistosoma mansoni infection in mice depleted of thymus-dependent lymphocytes. II. Pathology and altered pathogenesis. Am. J. Pathol., 1973. 71: 207 - 218.
16. SM Phillips, JJ DiConza, et al. Schistosomiasis in the congenitally athymic (nude) mouse: I. Thymic dependency of eosinophilia, granuloma formation, and host morbidity. J. Immunol, 1977. 118: 594-599.
17. EO Domingo and KS Warren. The inhibition of granuloma formation around Schistosoma mansoni eggs. II. Thymectomy. Am. J. Pathol, 1967. 51: 757-767.
18. DL Boros and KS Warren. Delayed hypersensitivity-type granuloma formation and dermal reaction induced and elicited by a soluble factor isolated from schistosoma mansoni eggs. J. Exp. Med, 1970. 132: 488-507.
19. HJ Hernandez, Y Wang, et al. Expression of class II, but not class I, majorhistocompatibility complex molecules is required for granuloma formation in infection with Schistosoma mansoni. Eur J Immunol, 1997. 27: 1170–1176.
20. VR Oliveira, MC El-Cheikh, et al. Schistosoma mansoni egg-induced hepatic granulomas in mice deficient for the interferon-γreceptor have altered populations of macrophages, lymphocytes and connective tissue cells. Microbes Infect, 2000. 2: 1817-1826.
21. EJ Pearce, P Caspar, et al. Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med, 1991. 173: 159-166.
22. JM Grzych, E Pearce, et al. Egg deposition is the major stimulus for the production of Th2 cytokines in murine schistosomiasis mansoni. J Immunol, 1991. 146:1322-1327.
23. EO Domingo and KS Warren. Endogenous desensitization: changing host granulomatou response to schistosome eggs at different stages of infection with schistosoma mansoni. Am J Pathol, 1968. 52: 369-379.
24. KS Warren, DI Grove, et al. The Schistosoma japonicum egg granuloma: II. Cellular composition, granuloma size, and immunologic concomitants. Am J Trop Med Hyg, 1978. 27: 271-275.
25. DL Boros, RP Pelley, et al. Spontaneous modulation of granulomatous hypersensitivity in schistosomiasis mansoni. J Immunol, 1975. 114: 1437-1441.
26. KS Warren. Modulation of immunopathology and disease in schistosomiasis. Am J Trop Med Hyg, 1977. 26: 113-119.
27. PG Fallon and DW Dunne. Tolerization of mice to Schistosoma mansoni egg antigens causes elevated type 1 and diminished type 2 cytokine responses and increased mortality in acute infection. J Immunol, 1999. 162: 4122-4132.
28. X Zheng, X Hu, et al. Soluble egg antigen from Schistosoma japonicummodulates the progression of chronic progressive experimental autoimmune encephalomyelitis via Th2-shift response. J Neuroimmunol, 2008. 194: 107-14.
29. AB Stavitsky. Regulation of granulomatous inflammation in experimental models of schistosomiasis. Infect Immun, 2004. 72: 1-12.
30. MY Gerner, KA Casey, et al. Defective MHC Class II Presentation by Dendritic Cells Limits CD4 T Cell Help for Antitumor CD8 T Cell Responses. J. Immunol., 2008. 181: 155 - 164.
31. CCB Jones, CN Kreklywich, et al. Rat cytomegalovirus infection depletes MHC II in bone marrow derived dendritic cells. Virology, 2009. 388(1): 78-90.
32. ND Pecora, SA Fulton, et al. Mycobacterium bovis BCG decreases MHC-II expression in vivo on murine lung macrophages and dendritic cells during aerosol infection. Cell Immunol, 2009. 254(2): 94-104.
33. S Redpath, A Angulo, et al. Murine Cytomegalovirus Infection Down-Regulates MHC Class II Expression on Macrophages by Induction of IL-10. J. Immunol., 1999. 162: 6701 - 6707.
34. RS Chu, D Askew, et al. CpG Oligodeoxynucleotides Down-Regulate Macrophage Class II MHC Antigen Processing. J. Immunol., 1999. 163: 1188 - 1194.
35. CG Luder, W Walter, et al. Toxoplasma gondii down-regulates MHC class II gene expression and antigen presentation by murine macrophages via interference with nuclear translocation of STAT1alpha. Eur J Immunol, 2001. 31(5): 1475-84.
36. B Namangala, L Brys, et al. Trypanosoma brucei brucei infection impairs MHC class II antigen presentation capacity of macrophages. Parasite Immunol, 2000. 22(7): 361-70.
37. S Han, K Kim, et al. Auranofin, an immunosuppressive drug, inhibits MHC class I and MHC class II pathways of antigen presentation in dendritic cells. ArchPharm Res, 2008. 31(3): 370-6.
38. H Sato and H Kamiya. Accelerated influx of dendritic cells into the lymph nodes draining skin sites exposed to attenuated cercariae of Schistosoma mansoni in guinea-pigs. Parasite Immunol, 1998. 20(7): 337-43.
39. H Sato and H Kamiya. Defect of protective immunity to Schistosoma mansoni infection in Mongolian gerbils involves limited recruitment of dendritic cells in the vaccinated skin. Parasite Immunol, 2001. 23(12): 627-32.
40. MJ Stadecker, JA Wright. Distribution and kinetics of mononuclear phagocytes in granulomas elicited by eggs of Schistosoma mansoni. Am J Pathol, 1984. 116:245-252.
41. JP Dalton and M Strand. Schistosoma mansoni polypeptides immunogenic in mice vaccinated with radiation-attenuated cercariae. J. Immunol., 1987. 139: 2474 - 2481.
42. H Li, XG Chen, et al. Preliminary study of cercaria antigen of Schistosoma japonicum before and after ultraviolet irradiation. 2002. 22(8): 697-9.
43. LL Yang, ZY Lv, et al. Schistosoma japonicum: proteomics analysis of differentially expressed proteins from ultraviolet-attenuated cercariae compared to normal cercariae. Parasitol Res, 2009. 105(1): 237-48.
44. BL Mangold and DA Dean. Passive transfer with serum and IgG antibodies of irradiated cercaria- induced resistance against Schistosoma mansoni in mice. J. Immunol., 1986. 136: 2644 - 2648.
45. K Sendide, A-E Deghmane, et al. Mycobacterium bovis BCG attenuates surface expression of mature class II molecules through IL-10-dependent inhibition of cathepsin S. J. Immunol, 2005. 175: 5324-5332.
46. DW Dunne and A Cooke. A worm’s eye view of the immune system: consequences for evolution of human autoimmune disease. Nat Rew Immunol,
2005. 5: 420-426.
47. DR Herbert, T Orekov, et al. IL-10 and TGF-beta redundantly protect against severe liver injury and mortality during acute schistosomiasis. J. Immunol, 2008. 181: 7214-7220.
48. LB Schook, SR Wellhausen, et al. Accessory cell function of liver granuloma macrophages of Schistosoma mansoni-infected mice. Infect. Immun, 1983. 42: 882-886.
49. AA Delvig, JJ Lee, et al. TGF-?1 and IFN- cross-regulate antigen presentation to CD4+T cells by macrophages. J. Leukoc. Biol, 2002. 72: 163-166.
50. EZ Kincaid, AJ Wolf, et al. Codominance of TLR2-dependent and TLR2-independent modulation of MHC class II in Mycobacterium tuberculosis infection in vivo. J. Immunol, 2007. 179: 3187-3195.
51. K Schroder, PJ Hertzog, et al. Interferon- : an overview of signals, mechanisms and functions. J. Leukoc. Biol, 2004. 75: 163-189.
52. U Boehm, T Klamp, et al. Cellular responses to interferon-γ. Annu Rev Immunol, 1997. 15: 749-795.
53. SP Saunders, CM Walsh, et al. The C-type lectin SIGNR1 binds Schistosoma mansoni antigens in vitro, but SIGNR1-deficient mice have normal responses during schistosome infection. Infect. Immun, 2009. 77: 399-404.
54. DVD Kleij, E Latz, et al. A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates Toll-like receptor 2 and affects immune polarization. J. Biol. Chem, 2002. 277: 48122-48129.
55. PG Thomas, MR Carter, et al. Maturation of dendritic cell 2 phenotype by a helminth glycan uses a Toll-like receptor 4-dependent mechanism. J. Immunol, 2003. 171: 5837-5841.
56. E Aksoy, CS Zouain, et al. Double-stranded RNAs from the helminth parasiteschistosoma activate TLR3 in dendritic cells. J. Biol. Chem, 2005. 280: 277-283.
57. K Takeda and S Akira. Toll-like receptors in innate immunity. Int. Immunol, 2005. 17: 1-14.
58. V Steimle , LA Otten , et al. Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome). Cell, 1993. 75: 135-146.
59. CH Chang, JD Fontes, et al. Class II transactivator (CIITA) is sufficient for the inducible expression of major histocompatibility complex class II genes. J. Exp. Med, 1994. 180: 1367-1374.
60. V Steimle, CA Siegrist, et al. Regulation of MHC class II expression by interferon-γmediated by the transactivator gene CIITA. Science, 1994. 265: 106-109.
61. DJ Weiss, OA Evanson, et al. Regulation of expression of major histocompatibility antigens by bovine macrophages infected with Mycobacterium avium subsp. paratuberculosis or Mycobacterium avium subsp. avium. Infect. Immun, 2001. 69: 1002-1008.
62. NE Reiner, W Ng, et al. Parasite-accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage expression of class I and class II major histocompatibility complex gene products. J. Immunol, 1987. 138: 1926-1932.
63. MT Heise, M Connick, et al. Murine Cytomegalovirus inhibits interferon–induced antigen presentation to CD4+ T cells by macrophages via regulation of expression of major histocompatibility complex class II–associated genes. J. Exp. Med, 1998. 187: 1037-1046.
64. CW Czarniecki, HH Chiu, et al. Transforming growth factor-beta 1 modulates the expression of class II histocompatibility antigens on human cells. J. Immunol,1988. 140: 4217-4223.
65. C Devajyothi, I Kalvakolanu, et al. Inhibition of interferon-γ-induced major histocompatibility complex class II gene transcription by interferon-beta and type beta 1 transforming growth factor in human astrocytoma cells. Definition of cis-element. J Biol Chem, 1993. 268: 18794-18800.
66. KN Couper, Blount DG, et al. IL-10: The master regulator of immunity to infection. J Immunol, 2008. 180: 5771-5777.
67. Farah IO, Mola PW, et al. Repeated exposure induces periportal fibrosis in Schistosoma mansoni-infected baboons: role of TGF-? and IL-4. J Immunology, 2000. 164: 5337-5343.
68. Kriegel MA, Li MO, et al. Transforming growth factor-beta: recent advances on its role in immune tolerance. Curr Rheumatol Rep, 2006. 8: 138-144.
69. Rakasz E, Blum AM, et al. Localization and regulation of IFN- production within the granulomas of murine schistosomiasis in IL-4-deficient and control mice. J Immunol, 1998. 160: 4994-4999.
70. Hoffmann KF, Cheever AW, et al. IL-10 and the dangers of immune polarization: Excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis. J Immunol, 2000. 164: 6406-6416.
71. Oswald IP, Wynn TA, et al. Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor required as a costimulatory factor for interferon -induced activation. PNAS, 1992. 89: 8676-8680.
72. Malefyt RDW, Haanen J, et al. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med, 1991. 174: 915-924.
73. Brandes ME, Mai UE, et al. Type I transforming growth factor-beta receptors on neutrophils mediate chemotaxis to transforming growth factor-beta. J. Immunol, 1991. 147: 1600-1606.
74. Luttmann W, Franz P, et al. Effects of TGF-beta on eosinophil chemotaxis. Scand J Immunol, 1998. 47: 127-30.
75. Li MO, Wan YY, et al. T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity, 2007. 26: 579-591.
76. Peng YF, Laouar Y, et al. TGF- regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes. PNAS, 2004. 101: 4572-4577.
77. Fantini MC, Becker C, et al. Cutting edge: TGF- induces a regulatory phenotype in CD4+CD25– T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol, 2004. 172: 5149-5153.
78. McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity, 2008. 28: 445-453.
79. Bettelli E, Carrier Y, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature, 2006. 441: 235-238.
80. Flamme ACL, MacDonald AS, et al. Role of IL-6 in directing the initial immune response to schistosome eggs. J Immunol, 2000. 164: 2419-2426.
81. Berger AC, Roche PA. MHC class II transport at a glance. J Cell Sci, 2009. 122: 1-4.
82. Ohmura-Hoshino M, Matsuki Y, et al. Cutting edge: requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance of conventional dendritic cells. J Immunol, 2009. 183: 6893-6897.
83. Mueller T, Terada T, et al. Th2 cytokines down-regulate TLR expression andfunction in human intestinal epithelial cells. J Immunol, 2006. 176: 5805-5814.
84. Miller LS, S?rensen OE, et al. TGF-αregulates TLR expression and function on epidermal keratinocytes. J Immunol, 2005. 174: 6137-6143.
85. Babu S, Blauvelt CP, et al. Diminished expression and function of TLR in lymphatic filariasis: A novel mechanism of immune dysregulation. J Immunol, 2005. 175: 1170-1176.
86. Rolland A, Jouvin-Marche E, et al. The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14/TLR4 and promotes Th1-like responses. J Immunol, 2006. 176: 7636-7644.
87. Oliveira A-C, Peixoto JR, et al. Expression of functional TLR4 confers proinflammatory responsiveness to Trypanosoma cruzi glycoinositolphospholipids and higher resistance to infection with T. cruzi. J Immunol, 2004. 173: 5688-5696.
88. M F Stek, P Minard, et al. Immunization of Baboons with Schistosoma mansoni Cercariae attenuated byγirradiation. Science, 1981. 212: 1518– 1520.
89. YE Shi, CF Jiang, et al. Immunization of pigs against infection with Schistosoma japonicum using ultraviolet-attenuated cercariae. Parasitology, 1993. 106: 459-62.
90. YE Shi, CF Jiang, et al. Schistosoma japonicum: an ultraviolet-attenuated cercarial vaccine applicable in the field for water buffaloes. Exp Parasitol, 1990. 71(1): 100-6.
91. R el Ridi, T Ozaki, et al. Immunization of mice with ultraviolet-attenuated cercariae of Schistosoma mansoni transiently reduces the fecundity of challenge worms. Int J Parasitol, 1997. 27(5): 581-6.
92. RA Wilson, PS Coulson, et al. Migration of the schistosomula of Schistosoma mansoni in mice vaccinated with radiation-attenuated cercariae, and normal mice: an attempt to identify the timing and site of parasite death. Parasitology, 1986. 92 :101-16.
93. R Harrop and RA Wilson. Irradiation of Schistosoma mansoni cercariae impairs neuromuscular function in developing schistosomula. J Parasitol, 1993. 79(2): 286-9.
94. JP Hewitson, PA Hamblin, et al. Immunity induced by the radiation-attenuated schistosome vaccine. Parasite Immunol, 2005. 27(7-8): 271-80.
95. A Sher, D Fiorentino, et al. Production of IL-10 by CD4+ T lymphocytes correlates with down- regulation of Th1 cytokine synthesis in helminth infection. J. Immunol., 1991. 147: 2713 - 2716.
96. CA Hall, MD Eugenio, et al. Schistosoma mansoni: antigen-presenting cells emigrating from skin exposed to attenuated cercariae activate lymphoid cells and transfer protection in C57B1/6 mice. J Parasitol, 2004. 90(4): 733-9.
97. DA Dean, MA Bukowski, et al. Attempts to Transfer the Resistance of Schistosoma Mansoni-Infected and Irradiated Cercaria-Immunized Mice by Means of Parabiosis. Am J Trop Med Hyg, 1981. 30: 113 - 120.
98. JP Dalton, M Strand, et al. Identification of Schistosoma mansoni glycoproteins recognized by protective antibodies from mice immunized with irradiated cercariae. J. Immunol., 1986. 136: 4689 - 4694.
99. W Wojciechowski, J DeSanctis, et al. Attenuation of MHC Class II Expression in Macrophages Infected with Mycobacterium bovis Bacillus Calmette-Guerin Involves Class II Transactivator and Depends on the Nramp1 Gene. J. Immunol., 1999. 163: 2688 - 2696.
100. S Kumkate, GR Jenkins, et al. CD207+ Langerhans cells constitute a minor population of skin-derived antigen-presenting cells in the draining lymph node following exposure to Schistosoma mansoni. Int J Parasitol, 2007. 37(2): 209-20.
101. TA Wynn, IP Oswald, et al. Elevated expression of Th1 cytokines and nitricoxide synthase in the lungs of vaccinated mice after challenge infection with Schistosoma mansoni. J. Immunol., 1994. 153: 5200 - 5209.
102. P Kourilová, KG Hogg, et al. Cercarial Dermatitis Caused by Bird Schistosomes Comprises Both Immediate and Late Phase Cutaneous Hypersensitivity Reactions. J. Immunol., 2004. 172: 3766 - 3774.
103. P Kumar and K Ramaswamy. Vaccination with irradiated cercariae of Schistosoma mansoni preferentially induced the accumulation of interferon-γproducing T cells in the skin and skin draining lymph nodes of mice. Parasitol Int, 1999. 48(2): 109-19.
104. TA Wynn, D Jankovic, et al. IL-12 enhances vaccine-induced immunity to Schistosoma mansoni in mice and decreases T helper 2 cytokine expression, IgE production, and tissue eosinophilia. J. Immunol., 1995. 154: 4701 - 4709.
105. LE Smythies, PS Coulson, et al. Monoclonal antibody to IFN-γmodifies pulmonary inflammatory responses and abrogates immunity to Schistosoma mansoni in mice vaccinated with attenuated cercariae. J. Immunol., 1992. 149: 3654 - 3658.
106. A Sher, RL Coffman, et al. Ablation of eosinophil and IgE responses with anti-IL-5 or anti-IL-4 antibodies fails to affect immunity against Schistosoma mansoni in the mouse. J Immunol, 1990. 145(11):3911–3916.
107. CL King, I Malhotra, et al. Schistosoma mansoni: Protective immunity in IL-4-deficient mice. Exp Parasitol, 1996. 84(2): 245–252.
108. IL Dodge, MW Carr, et al. IL-6 Production by Pulmonary Dendritic Cells Impedes Th1 Immune Responses. J. Immunol., 2003. 170: 4457 - 4464.
109. RT Gazzinelli, IP Oswald, et al. IL-10 inhibits parasite killing and nitrogen oxide production by IFN-γ-activated macrophages. J. Immunol., 1992. 148: 1792 - 1796.
110. TA Wynn, AW Cheever, et al. IL-10 Regulates Liver Pathology in Acute Murine Schistosomiasis mansoni But Is Not Required for Immune Down-Modulation of Chronic Disease. J. Immunol., 1998. 160: 4473 - 4480.
111. H Jing, E Vassiliou, et al. Prostaglandin E2 inhibits production of the inflammatory chemokines CCL3 and CCL4 in dendritic cells. J. Leukoc. Biol., 2003. 74: 868.
112. F Rousset, RW Malefijt, et al. Regulation of Fc receptor for IgE (CD23) and class II MHC antigen expression on Burkitt's lymphoma cell lines by human IL-4 and IFN-γ. J. Immunol., 1988. 140: 2625 - 2632.
113. F Figueiredo, RJ Uhing, et al. Activation of the cAMP cascade inhibits an early event involved in murine macrophage Ia expression. J. Biol. Chem., 1990. 265: 12317 - 12323.
114. BS Polla, A Poljak, et al. Regulation of class II gene expression: analysis in B cell stimulatory factor 1-inducible murine pre-B cell lines. J. Immunol., 1986. 137: 3332 - 3337.
115. K Ramaswamy, P Kumar, et al. A Role for Parasite-Induced PGE2 in IL-10-Mediated Host Immunoregulation by Skin Stage Schistosomula of Schistosoma mansoni. J. Immunol., 2000. 165: 4567 - 4574.
116. DV Moore and JH Sandground. The Relative Egg Producing Capacity of Schistosoma Mansoni and Schistosoma Japonicum. Am J Trop Med Hyg, 1956. 5: 831-840.
117. M Lukwiya, G Rizzardini, et al. Evaluation of immune activation in HIV-infected and uninfected African individuals by single-cell analysis of cytokine production. J Acquir Immune Defic Syndr, 2001; 28: 429-36.
118. DN Silva-Teixeira, C Contigli, et al. Cytokine profile associated to effector functions of human T cell clones specific for Schistosoma mansoni antigens. HumImmunol, 1998; 59: 219-224.
119. AL Graham. When T-helper cells don't help: immunopathology during concomitant infection. Q Rev Biol, 2002; 77: 409-434.
120. JA Pedras-Vasconcelos and EJ Pearce. Type 1 CD8+ T cell responses during infection with the helminth Schistosoma mansoni. J. Immunol., 1996; 157: 3046 - 3053.
121. CM Kane, L Cervi, et al. Helminth Antigens Modulate TLR-Initiated Dendritic Cell Activation. J. Immunol., 2004; 173: 7454 - 7461.
122. DE Elliott, S Ragheb, et al. Interactions between adherent mononuclear cells and lymphocytes from granulomas of mice with schistosomiasis mansoni. Infect. Immun., 1990; 58: 1577 - 1583.
123. SJ Jenkins and AP Mountford. Dendritic Cells Activated with Products Released by Schistosome Larvae Drive Th2-Type Immune Responses, Which Can Be Inhibited by Manipulation of CD40 Costimulation. Infect. Immun., 2005; 73: 395 - 402.
124. S Ferret-Bernard, RS Curwen, et al., Proteomic profiling reveals that Th2-inducing dendritic cells stimulated with helminth antigens have a 'limited maturation' phenotype. Proteomics, 2008; 8: 980-993.
125. ME Williams, S Montenegro, et al., Leukocytes of patients with Schistosoma mansoni respond with a Th2 pattern of cytokine production to mitogen or egg antigens but with a Th0 pattern to worm antigens. J Infect Dis, 1994; 170: 946-954.
1. I Amaldi, W Reith, et al. Induction of HLA class II genes by IFN-γis transcriptional and requires a trans-acting protein. J. Immunol., 1989. 142: 999 - 1004.
2. PA Sherman, PV Basta, et al. Upstream DNA Sequences Required for Tissue-Specific Expression of the HLA-DR Gene. PNAS, 1987. 84: 4254 - 4258.
3. JM Boss and JL Strominger. Regulation of a Transfected Human Class II Major Histocompatibility Complex Gene in Human Fibroblasts. PNAS, 1986. 83: 9139 - 9143.
4. SY Tsang, M Nakanishi, et al. Mutational analysis of the DRA promoter: cis-acting sequences and trans-acting factors. Mol. Cell. Biol., 1990. 10: 711 - 719.
5. KL Wright and JP Ting. In vivo Footprint Analysis of the HLA-DRA Gene Promoter: Cell-Specific Interaction at the Octomer Site and Up-Regulation of X Box Binding by Interferon . PNAS, 1992. 89: 7601 - 7605.
6. KL Wright, BJ Vilen, et al. CCAAT box binding protein NF-Y facilitates in vivo recruitment of upstream DNA binding transcription factors. EMBO, 1994. 13: 4042– 4053.
7. DK Didier, J Schiffenbauer, et al. Characterization of the cDNA Encoding a Protein Binding to the Major Histocompatibility Complex Class II Y Box. PNAS, 1988; 85: 7322 - 7326.
8. JP Ting, A Painter, et al. YB-1 DNA-binding protein represses interferon gamma activation of class II major histocompatibility complex genes. J. Exp. Med., 1994; 179: 1605.
9. Z Song, S Krishna, et al. A novel cysteine-rich sequence-specific DNA-binding protein interacts with the conserved X-box motif of the human major histocompatibility complex class II genes via a repeated Cys-His domain and functions as a transcriptional repressor. J. Exp. Med, 1994. 180: 1763-1774.
10. V Steimle, LA Otten, et al. Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome). Cell, 1993; 75(1): 135-46.
11. SA Abdulkadir, S Krishna, et al. Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression. J. Exp. Med., 1995; 182: 487.
12. NVD Stoep, E Quinten, et al. Transcriptional Regulation of the MHC Class II Trans-Activator (CIITA) Promoter III: Identification of a Novel Regulatory Region in the 5'-Untranslated Region and an Important Role for cAMP-Responsive Element Binding Protein 1 and Activating Transcription Factor-1 in CIITA-Promoter III Transcriptional Activation in B Lymphocytes. J. Immunol., 2002. 169: 5061 - 5071.
13. S Kanazawa and BM Peterlin. Combinations of dominant-negative class II transactivator, p300 or CDK9 proteins block the expression of MHC II genes. Int. Immunol., 2001; 13: 951 - 958.
14. CH Chang, S Guerder, et al. Mice lacking the MHC class II transactivator (CIITA) show tissue-specific impairment of MHC class II expression. Immunity,1996. 4:167.
15. V Steimle, CA Siegrist, et al. Regulation of MHC class II expression by interferon-γmediated by the transactivator gene CIITA. Science, 1994. 265: 106 - 109.
16. W Reith, B Mach. The bare lymphocyte syndrome and the regulation of MHCexpression. Annu. Rev. Immunol, 2001. 19:331.
17. JA Harton, JP Ting. Class II transactivator: mastering the art of major histocompatibility complex expression. Mol. Cell. Biol, 2000. 20:6185.
18. CH Chang, JD Fontes, et al. Class II transactivator (CIITA) is sufficient for the inducible expression of major histocompatibility complex class II genes. J. Exp. Med., 1994; 180: 1367.
19. LC Andersen, JS Beaty, et al. Allelic polymorphism in transcriptional regulatory regions of HLA-DQB genes. J. Exp. Med., 1991; 173: 181.
20. PR Wolf and HL Ploegh. Antigen presentation. DM exchange mechanism. Nature, 1995. 376(6540): 464-5.
21. EM Hiltbold and PA Roche. Trafficking of MHC class II molecules in the late secretory pathway. Curr Opin Immunol, 2002. 14(1): 30-5.
22. R Busch, CH Rinderknecht, et al. Achieving stability through editing and chaperoning: regulation of MHC class II peptide binding and expression. Immunol Rev, 2005. 207: 242-60.
23. LC Hsing, AY Rudensky. The lysosomal cysteine proteases in MHC class II antigen presentation. Immunol Rev, 2005. 207: 229-41.
24. AV Chervonsky and L Gordon. A segment of the MHC class IIβchain plays a critical role in targeting class II molecules to the endocytic pathway. International Immunology, 1994. 6: 973-982.
25. SJ Ono, E Colle, et al. Interferon-γinduces transcription and differential expression of MHC genes in rat insulinoma cell line RINm5F. Diabetes, 1989. 38: 911 - 916.
26. AD Gassart, V Camosseto, et al. MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. PNAS, 2008. 105: 3491 - 3496.
27. F Koch, U Stanzl, et al. High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10. J Exp Med, 1996. 184: 741.
28. H Cao, RG Wolff, et al. Differential regulation of class II MHC determinants on macrophages by IFN-γand IL-4. J. Immunol., 1989. 143: 3524 - 3531.
29. F Rousset, RW Malefijt, et al. Regulation of Fc receptor for IgE (CD23) and class II MHC antigen expression on Burkitt's lymphoma cell lines by human IL-4 and IFN-γ. J. Immunol., 1988. 140: 2625-2632.
30. EJ Gosselin, K Wardwell, et al. Induction of MHC class II on human polymorphonuclear neutrophils by granulocyte/macrophage colony-stimulating factor, IFN-gamma, and IL-3. J. Immunol., 1993; 151: 1482 - 1490.
31. RM Rapha?lle, F Mo?ra, et al. Regulation of MHC Class II Expression and Antigen Processing in Murine and Human Mesenchymal Stromal Cells by IFN- , TGF- , and Cell Density. J. Immunol., 2007. 179: 1549 - 1558.
32. RB Panek, YJ Lee, et al. TGF-βsuppression of IFN-γ-induced class II MHC gene expression does not involve inhibition of phosphorylation of JAK1, JAK2, or signal transducers and activators of transcription, or modification of IFN-γenhanced factor X expression. J. Immunol., 1995. 154: 610 - 619.
33. RB Panek and EN Benveniste J. Class II MHC gene expression in microglia. Regulation by the cytokines IFN-γ, TNF-alpha, and TGF-beta. Immunol., 1995. 154: 2846 - 2854.
34. C Benoist and D Mathis. Regulation of major histocompatibility complex class-II genes: X, Y and other letters of the alphabet. Annu Rev Immunol, 1990; 8: 681-715.
35. B Mach, V Steimle, et al. Regulation of MHC class II genes: lessons from a disease. Annu. Rev. Immunol, 1996. 14:301.
36. YL Han, ZHL Zhou, et al. TNF- Suppresses IFN- -Induced MHC Class II Expression in HT1080 Cells by Destabilizing Class II trans-Activator mRNA. J. Immunol., 1999; 163: 1435 - 1440.
37. DP King and PP Jones. Induction of Ia and H-2 antigens on a macrophage cell line by immune interferon. J. Immunol., 1983; 131: 315 - 318.
38. PM Stuart, A Zlotnik, et al. Induction of class I and class II MHC antigen expression on murine bone marrow-derived macrophages by IL-4 (B cell stimulatory factor 1). J. Immunol., 1988. 140: 1542 - 1547.
39. K Frei, H Lins, et al. Antigen presentation in the central nervous system. The inhibitory effect of IL-10 on MHC class II expression and production of cytokines depends on the inducing signals and the type of cell analyzed. J. Immunol., 1994. 152: 2720 - 2728.
40. YJ Lee, Y Han, et al. TGF-beta suppresses IFN-γinduction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression. J. Immunol., 1997. 158: 2065 - 2075.
41. YS Dong, LP Tang, et al. The Smad3 Protein Is Involved in TGF- Inhibition of Class II Transactivator and Class II MHC Expression. J. Immunol., 2001. 167: 311 - 319.
42. MA Meraz, JM White, et al. Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell, 1996. 84:431.
43. U Boehm, T Klamp, et al. Cellular responses to interferon-gamma. Annu Rev Immunol, 1997; 15: 749-95.
44. JC Marine, DJ Topham, et al. SOCS1 deficiency causes a lymphocyte dependent perinatal lethality. Cell, 1999. 98:609.
45. JC Marine, C McKay, et al. SOCS3 is essential in the regulation of fetal livererythropoiesis. Cell, 1999. 98:617.
46. D Metcalf, CJ Greenhalgh, et al. Gigantism in mice lacking suppressor of cytokine signalling-2. Nature, 2000. 405:1069.
47. T Naka, T Matsumoto, et al. Accelerated apoptosis of lymphocytes by augmented induction of Bax in SSI-1 (STAT-induced STAT inhibitor-1) deficient mice. Proc. Natl. Acad. Sci, 1998. 95:15577.
48. DL Krebs and DJ Hilton. SOCS: physiological suppressors of cytokine signaling. J. Cell Sci, 2000. 113:2813.
49. WS Alexander, R Starr, et al. SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell, 1999; 98(5): 597-608.
50. TA Endo, M Masuhara, et al. A new protein containing an SH2 domain that inhibits JAK kinases. Nature, 1997. 387:921.
51. T Naka, M Narazaki, et al. Structure and function of a new STAT-induced STAT inhibitor. Nature, 1997. 387:924.
52. M Narazaki, M Fujimoto, et al. Three distinct domains of SSI-1/SOCS-1/JAB protein are required for its suppression of interleukin 6 signaling. Proc. Natl. Acad. Sci, 1998. 95:13130.
53. SE Nicholson, TA Willson, et al. Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL-6 signal transduction. EMBO J, 1999. 18:375.
54. H Yasukawa, H Misawa, et al. The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. EMBO J, 1999. 18:1309.
55. S Hiroshi, Y Hideo, et al. A Janus Kinase Inhibitor, JAB, Is an Interferon--Inducible Gene and Confers Resistance to Interferons. Blood, 1998; 92: 1668 -1676.
56. R Starr, D Metcalf, et al. Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1. Proc. Natl. Acad. Sci, 1998. 95:14395.
57. MM Song and K Shuai. The Suppressor of Cytokine Signaling (SOCS) 1 and SOCS3 but Not SOCS2 Proteins Inhibit Interferon-mediated Antiviral and Antiproliferative Activities. J. Biol. Chem., 1998; 273: 35056.
58. S Ilangumaran, D Finan, et al. A Positive Regulatory Role for Suppressor of Cytokine Signaling 1 in IFN- -Induced MHC Class II Expression in Fibroblasts. J. Immunol., 2002; 169: 5010 - 5020.
59. CV Ramana, MP Gil, et al. Stat1-independent regulation of gene expression in response to IFN- . PNAS, 2001; 98: 6674 - 6679.
60. NS Trede, RS Geha, et al. Transcriptional activation of IL-1 beta and tumor necrosis factor-alpha genes by MHC class II ligands. J. Immunol., 1991; 146: 2310 - 2315.
61. L Lei, J Altstaedt, et al. Induction of interleukin-8 in human neutrophils after MHC class II cross-linking with superantigens. J. Leukoc. Biol., 2001; 70: 80.
62. IL Yoshie, JF Piskurich, et al. Reduced IL-4-, Lipopolysaccharide-, and IFN--Induced MHC Class II Expression in Mice Lacking Class II Transactivator Due to Targeted Deletion of the GTP-Binding Domain. J. Immuno, 1999, 163: 2425-2431.
63. W Rohn, LP Tang, et al. IL-1? Inhibits IFN- -Induced Class II MHC Expression by Suppressing Transcription of the Class II Transactivator Gene. J. Immunol., 1999; 162: 886 - 896.
64. TJ Sisk, T Gourley, et al. MHC Class II Transactivator Inhibits IL-4 Gene Transcription by Competing with NF-AT to Bind the Coactivator CREBBinding Protein (CBP)/p300. J. Immunol., 2000; 165: 2511 - 2517.
65. B Seddon and D Mason. Effects of cytokines and glucocorticoids on endogenous class II MHC antigen expression by activated rat CD4+ T cells. Mature CD4+CD8–thymocytes are phenotypically heterogeneous on activation. Int. Immunol., 1996; 8: 1185 - 1193.
66. RW Satola, SH Sanchez, et al. Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DR promoter binding protein, RF-X. Cell, 1988; 53, 897-906.
67. V Steimle, B Durand, et al. A novel DNA-binding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome). Genes & Dev., 1995; 9: 1021 - 1032.
68. EL Roy, MM Annick, et al. Escape of Human Cytomegalovirus from HLA-DR-Restricted CD4+ T-Cell Response Is Mediated by Repression of Gamma Interferon-Induced Class II Transactivator Expression. J. Virol., 1999; 73: 6582 - 6589.
69. GM Zhong, T Fan, et al. Chlamydia Inhibits Interferon–inducible Major Histocompatibility Complex Class II Expression by Degradation of Upstream Stimulatory Factor 1. J. Exp. Med., 1999; 189: 1931 - 1938.
70. GM Zhong, Li Liu, et al. Degradation of Transcription Factor Rfx5 during the Inhibition of Both Constitutive and Interferon–Inducible Major Histocompatibility Complex Class I Expression in Chlamydia-Infected Cells. J. Exp. Med., 2000; 191: 1525 - 1534.
71. X Zhu, S Pattenden, et al. pRB is required for interferon-gamma-induction of the MHC class II abeta gene. Oncogene, 1999; 18(35): 4940-7.
72. FE Borras, J Lloberas, et al. Repression of I-A gene expression by the transcription factor PU.1. J. Biol. Chem. 1995. 270:24385.
73. D. Choubey, SJ Li, et al. Inhibition of E2F-mediated transcription by p202. EMBO J, 1996. 15:5668.
74. W Min, S Ghosh, et al. The interferon-inducible p202 protein as a modulator of transcription: inhibition of NF-kappa B, c-Fos, and c-Jun activities. Mol. Cell. Biol., 1996; 16: 359 - 368.
75. C Hengstenberg, G Hufnagel, et al. De novo expression of MHC class I and class II antigens on endomyocardial biopsies from patients with inflammatory heart disease and rejection following heart transplantation. Eur Heart J, 1993.14:758-763.
76. CD Preval, MR Hadam, et al. Regulation of genes for HLA class 11 antigens in cell lines from patients isith severe combined iinmunodeficiency. N. EngI. J. Med. 1988. 318, 1295-1300
77. E Le, HQ Zhang, et al. CIITA Transformation Rescues the Apoptotic Function of MHC Class II in Melanoma Cells. Anticancer Res, 2005; 25: 3889 - 3892.
78. S Redpath, A Angulo, et al. Murine Cytomegalovirus Infection Down-Regulates MHC Class II Expression on Macrophages by Induction of IL-10. J. Immunol., 1999; 162: 6701 - 6707.
79. CK Baumgartner, A Ferrante. et al. Peptide-MHCclass II complex stability governs CD4 T cell clonal selection. J. Immuno. 2010.184:573-581.
2. MJ Ji, C Su, et al. Gene expression profile of CD4+ T cells reveals an interferon signaling suppression associated with progression of experimental Schistosoma japonicum infection. Cell Immunol, 2003. 224(1): 55-62.
3. MJ Ji, C Su, et al. Characterization of CD4~+ T Cell Responses in Mice Infected with Schistosoma japonicum. Acta Biochim Biophys Sin, 2006. 38: 327 - 334.
4. RA Wilson and PS Coulson. Why don't we have a schistosomiasis vaccine? Parasitol Today, 1998. 14(3): 97-9.
5. RA Wilson, PS Coulson, et al. Immune responses to the radiation-attenuated schistosome vaccine: what can we learn from knock-out mice? Immunol Lett, 1999. 65(1-2): 117-23.
6. DA Vignali, P Crocker, et al. A role for CD4+ but not CD8+ T cells in immunity to Schistosoma mansoni induced by 20 krad-irradiated and Ro 11-3128-terminated infections. Immunology, 1989. 67(4): 466-72.
7. LE Smythies, RM Pemberton, et al. T cell-derived cytokines associated with pulmonary immune mechanisms in mice vaccinated with irradiated cercariae of Schistosoma mansoni. J. Immunol., 1992. 148: 1512-1518.
8. S Anderson, VL Shires, et al. In the absence of IL-12, the induction of Th1-mediated protective immunity by the attenuated schistosome vaccine is impaired, revealing an alternative pathway with Th2-type characteristics. Eur J Immunol, 1998. 28(9): 2827-38.
9. S Anderson, PS Coulson, et al. The radiation-attenuated schistosome vaccine induces high levels of protective immunity in the absence of B cells. Immunology, 1999. 96(1): 22-8.
10. EC Ratcliffe and RA Wilson. The role of mononuclear-cell recruitment to the lungs in the development and expression of immunity to Schistosoma mansoni. Parasitology, 1992. 104: 299-307.
11. JE Crabtree and RA Wilson. The role of pulmonary cellular reactions in the resistance of vaccinated mice to Schistosoma mansoni. Parasite Immunol, 1986. 8(3): 265-85.
12. RA Wilson, PS Coulson, et al. Impaired immunity and altered pulmonary responses in mice with a disrupted interferon-γreceptor gene exposed to the irradiated Schistosoma mansoni vaccine. Immunology, 1996. 87(2): 275-82.
13. Z Caulada-Benedetti, F al-Zamel, et al. Comparison of Th1- and Th2-associated immune reactivities stimulated by single versus multiple vaccination of mice with irradiated Schistosoma mansoni cercariae. J. Immunol., 1991. 146: 1655 - 1660.
14. KS Warren, EO Domingo, et al. Granuloma formation around schistosome eggs as a manifestation of delayed hypersensitivity. Am. J. Pathol., 1967. 51: 735 - 756.
15. RD Buchanan, DP Fine, et al. Schistosoma mansoni infection in mice depleted of thymus-dependent lymphocytes. II. Pathology and altered pathogenesis. Am. J. Pathol., 1973. 71: 207 - 218.
16. SM Phillips, JJ DiConza, et al. Schistosomiasis in the congenitally athymic (nude) mouse: I. Thymic dependency of eosinophilia, granuloma formation, and host morbidity. J. Immunol, 1977. 118: 594-599.
17. EO Domingo and KS Warren. The inhibition of granuloma formation around Schistosoma mansoni eggs. II. Thymectomy. Am. J. Pathol, 1967. 51: 757-767.
18. DL Boros and KS Warren. Delayed hypersensitivity-type granuloma formation and dermal reaction induced and elicited by a soluble factor isolated from schistosoma mansoni eggs. J. Exp. Med, 1970. 132: 488-507.
19. HJ Hernandez, Y Wang, et al. Expression of class II, but not class I, majorhistocompatibility complex molecules is required for granuloma formation in infection with Schistosoma mansoni. Eur J Immunol, 1997. 27: 1170–1176.
20. VR Oliveira, MC El-Cheikh, et al. Schistosoma mansoni egg-induced hepatic granulomas in mice deficient for the interferon-γreceptor have altered populations of macrophages, lymphocytes and connective tissue cells. Microbes Infect, 2000. 2: 1817-1826.
21. EJ Pearce, P Caspar, et al. Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med, 1991. 173: 159-166.
22. JM Grzych, E Pearce, et al. Egg deposition is the major stimulus for the production of Th2 cytokines in murine schistosomiasis mansoni. J Immunol, 1991. 146:1322-1327.
23. EO Domingo and KS Warren. Endogenous desensitization: changing host granulomatou response to schistosome eggs at different stages of infection with schistosoma mansoni. Am J Pathol, 1968. 52: 369-379.
24. KS Warren, DI Grove, et al. The Schistosoma japonicum egg granuloma: II. Cellular composition, granuloma size, and immunologic concomitants. Am J Trop Med Hyg, 1978. 27: 271-275.
25. DL Boros, RP Pelley, et al. Spontaneous modulation of granulomatous hypersensitivity in schistosomiasis mansoni. J Immunol, 1975. 114: 1437-1441.
26. KS Warren. Modulation of immunopathology and disease in schistosomiasis. Am J Trop Med Hyg, 1977. 26: 113-119.
27. PG Fallon and DW Dunne. Tolerization of mice to Schistosoma mansoni egg antigens causes elevated type 1 and diminished type 2 cytokine responses and increased mortality in acute infection. J Immunol, 1999. 162: 4122-4132.
28. X Zheng, X Hu, et al. Soluble egg antigen from Schistosoma japonicummodulates the progression of chronic progressive experimental autoimmune encephalomyelitis via Th2-shift response. J Neuroimmunol, 2008. 194: 107-14.
29. AB Stavitsky. Regulation of granulomatous inflammation in experimental models of schistosomiasis. Infect Immun, 2004. 72: 1-12.
30. MY Gerner, KA Casey, et al. Defective MHC Class II Presentation by Dendritic Cells Limits CD4 T Cell Help for Antitumor CD8 T Cell Responses. J. Immunol., 2008. 181: 155 - 164.
31. CCB Jones, CN Kreklywich, et al. Rat cytomegalovirus infection depletes MHC II in bone marrow derived dendritic cells. Virology, 2009. 388(1): 78-90.
32. ND Pecora, SA Fulton, et al. Mycobacterium bovis BCG decreases MHC-II expression in vivo on murine lung macrophages and dendritic cells during aerosol infection. Cell Immunol, 2009. 254(2): 94-104.
33. S Redpath, A Angulo, et al. Murine Cytomegalovirus Infection Down-Regulates MHC Class II Expression on Macrophages by Induction of IL-10. J. Immunol., 1999. 162: 6701 - 6707.
34. RS Chu, D Askew, et al. CpG Oligodeoxynucleotides Down-Regulate Macrophage Class II MHC Antigen Processing. J. Immunol., 1999. 163: 1188 - 1194.
35. CG Luder, W Walter, et al. Toxoplasma gondii down-regulates MHC class II gene expression and antigen presentation by murine macrophages via interference with nuclear translocation of STAT1alpha. Eur J Immunol, 2001. 31(5): 1475-84.
36. B Namangala, L Brys, et al. Trypanosoma brucei brucei infection impairs MHC class II antigen presentation capacity of macrophages. Parasite Immunol, 2000. 22(7): 361-70.
37. S Han, K Kim, et al. Auranofin, an immunosuppressive drug, inhibits MHC class I and MHC class II pathways of antigen presentation in dendritic cells. ArchPharm Res, 2008. 31(3): 370-6.
38. H Sato and H Kamiya. Accelerated influx of dendritic cells into the lymph nodes draining skin sites exposed to attenuated cercariae of Schistosoma mansoni in guinea-pigs. Parasite Immunol, 1998. 20(7): 337-43.
39. H Sato and H Kamiya. Defect of protective immunity to Schistosoma mansoni infection in Mongolian gerbils involves limited recruitment of dendritic cells in the vaccinated skin. Parasite Immunol, 2001. 23(12): 627-32.
40. MJ Stadecker, JA Wright. Distribution and kinetics of mononuclear phagocytes in granulomas elicited by eggs of Schistosoma mansoni. Am J Pathol, 1984. 116:245-252.
41. JP Dalton and M Strand. Schistosoma mansoni polypeptides immunogenic in mice vaccinated with radiation-attenuated cercariae. J. Immunol., 1987. 139: 2474 - 2481.
42. H Li, XG Chen, et al. Preliminary study of cercaria antigen of Schistosoma japonicum before and after ultraviolet irradiation. 2002. 22(8): 697-9.
43. LL Yang, ZY Lv, et al. Schistosoma japonicum: proteomics analysis of differentially expressed proteins from ultraviolet-attenuated cercariae compared to normal cercariae. Parasitol Res, 2009. 105(1): 237-48.
44. BL Mangold and DA Dean. Passive transfer with serum and IgG antibodies of irradiated cercaria- induced resistance against Schistosoma mansoni in mice. J. Immunol., 1986. 136: 2644 - 2648.
45. K Sendide, A-E Deghmane, et al. Mycobacterium bovis BCG attenuates surface expression of mature class II molecules through IL-10-dependent inhibition of cathepsin S. J. Immunol, 2005. 175: 5324-5332.
46. DW Dunne and A Cooke. A worm’s eye view of the immune system: consequences for evolution of human autoimmune disease. Nat Rew Immunol,
2005. 5: 420-426.
47. DR Herbert, T Orekov, et al. IL-10 and TGF-beta redundantly protect against severe liver injury and mortality during acute schistosomiasis. J. Immunol, 2008. 181: 7214-7220.
48. LB Schook, SR Wellhausen, et al. Accessory cell function of liver granuloma macrophages of Schistosoma mansoni-infected mice. Infect. Immun, 1983. 42: 882-886.
49. AA Delvig, JJ Lee, et al. TGF-?1 and IFN- cross-regulate antigen presentation to CD4+T cells by macrophages. J. Leukoc. Biol, 2002. 72: 163-166.
50. EZ Kincaid, AJ Wolf, et al. Codominance of TLR2-dependent and TLR2-independent modulation of MHC class II in Mycobacterium tuberculosis infection in vivo. J. Immunol, 2007. 179: 3187-3195.
51. K Schroder, PJ Hertzog, et al. Interferon- : an overview of signals, mechanisms and functions. J. Leukoc. Biol, 2004. 75: 163-189.
52. U Boehm, T Klamp, et al. Cellular responses to interferon-γ. Annu Rev Immunol, 1997. 15: 749-795.
53. SP Saunders, CM Walsh, et al. The C-type lectin SIGNR1 binds Schistosoma mansoni antigens in vitro, but SIGNR1-deficient mice have normal responses during schistosome infection. Infect. Immun, 2009. 77: 399-404.
54. DVD Kleij, E Latz, et al. A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates Toll-like receptor 2 and affects immune polarization. J. Biol. Chem, 2002. 277: 48122-48129.
55. PG Thomas, MR Carter, et al. Maturation of dendritic cell 2 phenotype by a helminth glycan uses a Toll-like receptor 4-dependent mechanism. J. Immunol, 2003. 171: 5837-5841.
56. E Aksoy, CS Zouain, et al. Double-stranded RNAs from the helminth parasiteschistosoma activate TLR3 in dendritic cells. J. Biol. Chem, 2005. 280: 277-283.
57. K Takeda and S Akira. Toll-like receptors in innate immunity. Int. Immunol, 2005. 17: 1-14.
58. V Steimle , LA Otten , et al. Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome). Cell, 1993. 75: 135-146.
59. CH Chang, JD Fontes, et al. Class II transactivator (CIITA) is sufficient for the inducible expression of major histocompatibility complex class II genes. J. Exp. Med, 1994. 180: 1367-1374.
60. V Steimle, CA Siegrist, et al. Regulation of MHC class II expression by interferon-γmediated by the transactivator gene CIITA. Science, 1994. 265: 106-109.
61. DJ Weiss, OA Evanson, et al. Regulation of expression of major histocompatibility antigens by bovine macrophages infected with Mycobacterium avium subsp. paratuberculosis or Mycobacterium avium subsp. avium. Infect. Immun, 2001. 69: 1002-1008.
62. NE Reiner, W Ng, et al. Parasite-accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage expression of class I and class II major histocompatibility complex gene products. J. Immunol, 1987. 138: 1926-1932.
63. MT Heise, M Connick, et al. Murine Cytomegalovirus inhibits interferon–induced antigen presentation to CD4+ T cells by macrophages via regulation of expression of major histocompatibility complex class II–associated genes. J. Exp. Med, 1998. 187: 1037-1046.
64. CW Czarniecki, HH Chiu, et al. Transforming growth factor-beta 1 modulates the expression of class II histocompatibility antigens on human cells. J. Immunol,1988. 140: 4217-4223.
65. C Devajyothi, I Kalvakolanu, et al. Inhibition of interferon-γ-induced major histocompatibility complex class II gene transcription by interferon-beta and type beta 1 transforming growth factor in human astrocytoma cells. Definition of cis-element. J Biol Chem, 1993. 268: 18794-18800.
66. KN Couper, Blount DG, et al. IL-10: The master regulator of immunity to infection. J Immunol, 2008. 180: 5771-5777.
67. Farah IO, Mola PW, et al. Repeated exposure induces periportal fibrosis in Schistosoma mansoni-infected baboons: role of TGF-? and IL-4. J Immunology, 2000. 164: 5337-5343.
68. Kriegel MA, Li MO, et al. Transforming growth factor-beta: recent advances on its role in immune tolerance. Curr Rheumatol Rep, 2006. 8: 138-144.
69. Rakasz E, Blum AM, et al. Localization and regulation of IFN- production within the granulomas of murine schistosomiasis in IL-4-deficient and control mice. J Immunol, 1998. 160: 4994-4999.
70. Hoffmann KF, Cheever AW, et al. IL-10 and the dangers of immune polarization: Excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis. J Immunol, 2000. 164: 6406-6416.
71. Oswald IP, Wynn TA, et al. Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor required as a costimulatory factor for interferon -induced activation. PNAS, 1992. 89: 8676-8680.
72. Malefyt RDW, Haanen J, et al. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med, 1991. 174: 915-924.
73. Brandes ME, Mai UE, et al. Type I transforming growth factor-beta receptors on neutrophils mediate chemotaxis to transforming growth factor-beta. J. Immunol, 1991. 147: 1600-1606.
74. Luttmann W, Franz P, et al. Effects of TGF-beta on eosinophil chemotaxis. Scand J Immunol, 1998. 47: 127-30.
75. Li MO, Wan YY, et al. T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity, 2007. 26: 579-591.
76. Peng YF, Laouar Y, et al. TGF- regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes. PNAS, 2004. 101: 4572-4577.
77. Fantini MC, Becker C, et al. Cutting edge: TGF- induces a regulatory phenotype in CD4+CD25– T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol, 2004. 172: 5149-5153.
78. McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity, 2008. 28: 445-453.
79. Bettelli E, Carrier Y, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature, 2006. 441: 235-238.
80. Flamme ACL, MacDonald AS, et al. Role of IL-6 in directing the initial immune response to schistosome eggs. J Immunol, 2000. 164: 2419-2426.
81. Berger AC, Roche PA. MHC class II transport at a glance. J Cell Sci, 2009. 122: 1-4.
82. Ohmura-Hoshino M, Matsuki Y, et al. Cutting edge: requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance of conventional dendritic cells. J Immunol, 2009. 183: 6893-6897.
83. Mueller T, Terada T, et al. Th2 cytokines down-regulate TLR expression andfunction in human intestinal epithelial cells. J Immunol, 2006. 176: 5805-5814.
84. Miller LS, S?rensen OE, et al. TGF-αregulates TLR expression and function on epidermal keratinocytes. J Immunol, 2005. 174: 6137-6143.
85. Babu S, Blauvelt CP, et al. Diminished expression and function of TLR in lymphatic filariasis: A novel mechanism of immune dysregulation. J Immunol, 2005. 175: 1170-1176.
86. Rolland A, Jouvin-Marche E, et al. The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14/TLR4 and promotes Th1-like responses. J Immunol, 2006. 176: 7636-7644.
87. Oliveira A-C, Peixoto JR, et al. Expression of functional TLR4 confers proinflammatory responsiveness to Trypanosoma cruzi glycoinositolphospholipids and higher resistance to infection with T. cruzi. J Immunol, 2004. 173: 5688-5696.
88. M F Stek, P Minard, et al. Immunization of Baboons with Schistosoma mansoni Cercariae attenuated byγirradiation. Science, 1981. 212: 1518– 1520.
89. YE Shi, CF Jiang, et al. Immunization of pigs against infection with Schistosoma japonicum using ultraviolet-attenuated cercariae. Parasitology, 1993. 106: 459-62.
90. YE Shi, CF Jiang, et al. Schistosoma japonicum: an ultraviolet-attenuated cercarial vaccine applicable in the field for water buffaloes. Exp Parasitol, 1990. 71(1): 100-6.
91. R el Ridi, T Ozaki, et al. Immunization of mice with ultraviolet-attenuated cercariae of Schistosoma mansoni transiently reduces the fecundity of challenge worms. Int J Parasitol, 1997. 27(5): 581-6.
92. RA Wilson, PS Coulson, et al. Migration of the schistosomula of Schistosoma mansoni in mice vaccinated with radiation-attenuated cercariae, and normal mice: an attempt to identify the timing and site of parasite death. Parasitology, 1986. 92 :101-16.
93. R Harrop and RA Wilson. Irradiation of Schistosoma mansoni cercariae impairs neuromuscular function in developing schistosomula. J Parasitol, 1993. 79(2): 286-9.
94. JP Hewitson, PA Hamblin, et al. Immunity induced by the radiation-attenuated schistosome vaccine. Parasite Immunol, 2005. 27(7-8): 271-80.
95. A Sher, D Fiorentino, et al. Production of IL-10 by CD4+ T lymphocytes correlates with down- regulation of Th1 cytokine synthesis in helminth infection. J. Immunol., 1991. 147: 2713 - 2716.
96. CA Hall, MD Eugenio, et al. Schistosoma mansoni: antigen-presenting cells emigrating from skin exposed to attenuated cercariae activate lymphoid cells and transfer protection in C57B1/6 mice. J Parasitol, 2004. 90(4): 733-9.
97. DA Dean, MA Bukowski, et al. Attempts to Transfer the Resistance of Schistosoma Mansoni-Infected and Irradiated Cercaria-Immunized Mice by Means of Parabiosis. Am J Trop Med Hyg, 1981. 30: 113 - 120.
98. JP Dalton, M Strand, et al. Identification of Schistosoma mansoni glycoproteins recognized by protective antibodies from mice immunized with irradiated cercariae. J. Immunol., 1986. 136: 4689 - 4694.
99. W Wojciechowski, J DeSanctis, et al. Attenuation of MHC Class II Expression in Macrophages Infected with Mycobacterium bovis Bacillus Calmette-Guerin Involves Class II Transactivator and Depends on the Nramp1 Gene. J. Immunol., 1999. 163: 2688 - 2696.
100. S Kumkate, GR Jenkins, et al. CD207+ Langerhans cells constitute a minor population of skin-derived antigen-presenting cells in the draining lymph node following exposure to Schistosoma mansoni. Int J Parasitol, 2007. 37(2): 209-20.
101. TA Wynn, IP Oswald, et al. Elevated expression of Th1 cytokines and nitricoxide synthase in the lungs of vaccinated mice after challenge infection with Schistosoma mansoni. J. Immunol., 1994. 153: 5200 - 5209.
102. P Kourilová, KG Hogg, et al. Cercarial Dermatitis Caused by Bird Schistosomes Comprises Both Immediate and Late Phase Cutaneous Hypersensitivity Reactions. J. Immunol., 2004. 172: 3766 - 3774.
103. P Kumar and K Ramaswamy. Vaccination with irradiated cercariae of Schistosoma mansoni preferentially induced the accumulation of interferon-γproducing T cells in the skin and skin draining lymph nodes of mice. Parasitol Int, 1999. 48(2): 109-19.
104. TA Wynn, D Jankovic, et al. IL-12 enhances vaccine-induced immunity to Schistosoma mansoni in mice and decreases T helper 2 cytokine expression, IgE production, and tissue eosinophilia. J. Immunol., 1995. 154: 4701 - 4709.
105. LE Smythies, PS Coulson, et al. Monoclonal antibody to IFN-γmodifies pulmonary inflammatory responses and abrogates immunity to Schistosoma mansoni in mice vaccinated with attenuated cercariae. J. Immunol., 1992. 149: 3654 - 3658.
106. A Sher, RL Coffman, et al. Ablation of eosinophil and IgE responses with anti-IL-5 or anti-IL-4 antibodies fails to affect immunity against Schistosoma mansoni in the mouse. J Immunol, 1990. 145(11):3911–3916.
107. CL King, I Malhotra, et al. Schistosoma mansoni: Protective immunity in IL-4-deficient mice. Exp Parasitol, 1996. 84(2): 245–252.
108. IL Dodge, MW Carr, et al. IL-6 Production by Pulmonary Dendritic Cells Impedes Th1 Immune Responses. J. Immunol., 2003. 170: 4457 - 4464.
109. RT Gazzinelli, IP Oswald, et al. IL-10 inhibits parasite killing and nitrogen oxide production by IFN-γ-activated macrophages. J. Immunol., 1992. 148: 1792 - 1796.
110. TA Wynn, AW Cheever, et al. IL-10 Regulates Liver Pathology in Acute Murine Schistosomiasis mansoni But Is Not Required for Immune Down-Modulation of Chronic Disease. J. Immunol., 1998. 160: 4473 - 4480.
111. H Jing, E Vassiliou, et al. Prostaglandin E2 inhibits production of the inflammatory chemokines CCL3 and CCL4 in dendritic cells. J. Leukoc. Biol., 2003. 74: 868.
112. F Rousset, RW Malefijt, et al. Regulation of Fc receptor for IgE (CD23) and class II MHC antigen expression on Burkitt's lymphoma cell lines by human IL-4 and IFN-γ. J. Immunol., 1988. 140: 2625 - 2632.
113. F Figueiredo, RJ Uhing, et al. Activation of the cAMP cascade inhibits an early event involved in murine macrophage Ia expression. J. Biol. Chem., 1990. 265: 12317 - 12323.
114. BS Polla, A Poljak, et al. Regulation of class II gene expression: analysis in B cell stimulatory factor 1-inducible murine pre-B cell lines. J. Immunol., 1986. 137: 3332 - 3337.
115. K Ramaswamy, P Kumar, et al. A Role for Parasite-Induced PGE2 in IL-10-Mediated Host Immunoregulation by Skin Stage Schistosomula of Schistosoma mansoni. J. Immunol., 2000. 165: 4567 - 4574.
116. DV Moore and JH Sandground. The Relative Egg Producing Capacity of Schistosoma Mansoni and Schistosoma Japonicum. Am J Trop Med Hyg, 1956. 5: 831-840.
117. M Lukwiya, G Rizzardini, et al. Evaluation of immune activation in HIV-infected and uninfected African individuals by single-cell analysis of cytokine production. J Acquir Immune Defic Syndr, 2001; 28: 429-36.
118. DN Silva-Teixeira, C Contigli, et al. Cytokine profile associated to effector functions of human T cell clones specific for Schistosoma mansoni antigens. HumImmunol, 1998; 59: 219-224.
119. AL Graham. When T-helper cells don't help: immunopathology during concomitant infection. Q Rev Biol, 2002; 77: 409-434.
120. JA Pedras-Vasconcelos and EJ Pearce. Type 1 CD8+ T cell responses during infection with the helminth Schistosoma mansoni. J. Immunol., 1996; 157: 3046 - 3053.
121. CM Kane, L Cervi, et al. Helminth Antigens Modulate TLR-Initiated Dendritic Cell Activation. J. Immunol., 2004; 173: 7454 - 7461.
122. DE Elliott, S Ragheb, et al. Interactions between adherent mononuclear cells and lymphocytes from granulomas of mice with schistosomiasis mansoni. Infect. Immun., 1990; 58: 1577 - 1583.
123. SJ Jenkins and AP Mountford. Dendritic Cells Activated with Products Released by Schistosome Larvae Drive Th2-Type Immune Responses, Which Can Be Inhibited by Manipulation of CD40 Costimulation. Infect. Immun., 2005; 73: 395 - 402.
124. S Ferret-Bernard, RS Curwen, et al., Proteomic profiling reveals that Th2-inducing dendritic cells stimulated with helminth antigens have a 'limited maturation' phenotype. Proteomics, 2008; 8: 980-993.
125. ME Williams, S Montenegro, et al., Leukocytes of patients with Schistosoma mansoni respond with a Th2 pattern of cytokine production to mitogen or egg antigens but with a Th0 pattern to worm antigens. J Infect Dis, 1994; 170: 946-954.
1. I Amaldi, W Reith, et al. Induction of HLA class II genes by IFN-γis transcriptional and requires a trans-acting protein. J. Immunol., 1989. 142: 999 - 1004.
2. PA Sherman, PV Basta, et al. Upstream DNA Sequences Required for Tissue-Specific Expression of the HLA-DR Gene. PNAS, 1987. 84: 4254 - 4258.
3. JM Boss and JL Strominger. Regulation of a Transfected Human Class II Major Histocompatibility Complex Gene in Human Fibroblasts. PNAS, 1986. 83: 9139 - 9143.
4. SY Tsang, M Nakanishi, et al. Mutational analysis of the DRA promoter: cis-acting sequences and trans-acting factors. Mol. Cell. Biol., 1990. 10: 711 - 719.
5. KL Wright and JP Ting. In vivo Footprint Analysis of the HLA-DRA Gene Promoter: Cell-Specific Interaction at the Octomer Site and Up-Regulation of X Box Binding by Interferon . PNAS, 1992. 89: 7601 - 7605.
6. KL Wright, BJ Vilen, et al. CCAAT box binding protein NF-Y facilitates in vivo recruitment of upstream DNA binding transcription factors. EMBO, 1994. 13: 4042– 4053.
7. DK Didier, J Schiffenbauer, et al. Characterization of the cDNA Encoding a Protein Binding to the Major Histocompatibility Complex Class II Y Box. PNAS, 1988; 85: 7322 - 7326.
8. JP Ting, A Painter, et al. YB-1 DNA-binding protein represses interferon gamma activation of class II major histocompatibility complex genes. J. Exp. Med., 1994; 179: 1605.
9. Z Song, S Krishna, et al. A novel cysteine-rich sequence-specific DNA-binding protein interacts with the conserved X-box motif of the human major histocompatibility complex class II genes via a repeated Cys-His domain and functions as a transcriptional repressor. J. Exp. Med, 1994. 180: 1763-1774.
10. V Steimle, LA Otten, et al. Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome). Cell, 1993; 75(1): 135-46.
11. SA Abdulkadir, S Krishna, et al. Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression. J. Exp. Med., 1995; 182: 487.
12. NVD Stoep, E Quinten, et al. Transcriptional Regulation of the MHC Class II Trans-Activator (CIITA) Promoter III: Identification of a Novel Regulatory Region in the 5'-Untranslated Region and an Important Role for cAMP-Responsive Element Binding Protein 1 and Activating Transcription Factor-1 in CIITA-Promoter III Transcriptional Activation in B Lymphocytes. J. Immunol., 2002. 169: 5061 - 5071.
13. S Kanazawa and BM Peterlin. Combinations of dominant-negative class II transactivator, p300 or CDK9 proteins block the expression of MHC II genes. Int. Immunol., 2001; 13: 951 - 958.
14. CH Chang, S Guerder, et al. Mice lacking the MHC class II transactivator (CIITA) show tissue-specific impairment of MHC class II expression. Immunity,1996. 4:167.
15. V Steimle, CA Siegrist, et al. Regulation of MHC class II expression by interferon-γmediated by the transactivator gene CIITA. Science, 1994. 265: 106 - 109.
16. W Reith, B Mach. The bare lymphocyte syndrome and the regulation of MHCexpression. Annu. Rev. Immunol, 2001. 19:331.
17. JA Harton, JP Ting. Class II transactivator: mastering the art of major histocompatibility complex expression. Mol. Cell. Biol, 2000. 20:6185.
18. CH Chang, JD Fontes, et al. Class II transactivator (CIITA) is sufficient for the inducible expression of major histocompatibility complex class II genes. J. Exp. Med., 1994; 180: 1367.
19. LC Andersen, JS Beaty, et al. Allelic polymorphism in transcriptional regulatory regions of HLA-DQB genes. J. Exp. Med., 1991; 173: 181.
20. PR Wolf and HL Ploegh. Antigen presentation. DM exchange mechanism. Nature, 1995. 376(6540): 464-5.
21. EM Hiltbold and PA Roche. Trafficking of MHC class II molecules in the late secretory pathway. Curr Opin Immunol, 2002. 14(1): 30-5.
22. R Busch, CH Rinderknecht, et al. Achieving stability through editing and chaperoning: regulation of MHC class II peptide binding and expression. Immunol Rev, 2005. 207: 242-60.
23. LC Hsing, AY Rudensky. The lysosomal cysteine proteases in MHC class II antigen presentation. Immunol Rev, 2005. 207: 229-41.
24. AV Chervonsky and L Gordon. A segment of the MHC class IIβchain plays a critical role in targeting class II molecules to the endocytic pathway. International Immunology, 1994. 6: 973-982.
25. SJ Ono, E Colle, et al. Interferon-γinduces transcription and differential expression of MHC genes in rat insulinoma cell line RINm5F. Diabetes, 1989. 38: 911 - 916.
26. AD Gassart, V Camosseto, et al. MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. PNAS, 2008. 105: 3491 - 3496.
27. F Koch, U Stanzl, et al. High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10. J Exp Med, 1996. 184: 741.
28. H Cao, RG Wolff, et al. Differential regulation of class II MHC determinants on macrophages by IFN-γand IL-4. J. Immunol., 1989. 143: 3524 - 3531.
29. F Rousset, RW Malefijt, et al. Regulation of Fc receptor for IgE (CD23) and class II MHC antigen expression on Burkitt's lymphoma cell lines by human IL-4 and IFN-γ. J. Immunol., 1988. 140: 2625-2632.
30. EJ Gosselin, K Wardwell, et al. Induction of MHC class II on human polymorphonuclear neutrophils by granulocyte/macrophage colony-stimulating factor, IFN-gamma, and IL-3. J. Immunol., 1993; 151: 1482 - 1490.
31. RM Rapha?lle, F Mo?ra, et al. Regulation of MHC Class II Expression and Antigen Processing in Murine and Human Mesenchymal Stromal Cells by IFN- , TGF- , and Cell Density. J. Immunol., 2007. 179: 1549 - 1558.
32. RB Panek, YJ Lee, et al. TGF-βsuppression of IFN-γ-induced class II MHC gene expression does not involve inhibition of phosphorylation of JAK1, JAK2, or signal transducers and activators of transcription, or modification of IFN-γenhanced factor X expression. J. Immunol., 1995. 154: 610 - 619.
33. RB Panek and EN Benveniste J. Class II MHC gene expression in microglia. Regulation by the cytokines IFN-γ, TNF-alpha, and TGF-beta. Immunol., 1995. 154: 2846 - 2854.
34. C Benoist and D Mathis. Regulation of major histocompatibility complex class-II genes: X, Y and other letters of the alphabet. Annu Rev Immunol, 1990; 8: 681-715.
35. B Mach, V Steimle, et al. Regulation of MHC class II genes: lessons from a disease. Annu. Rev. Immunol, 1996. 14:301.
36. YL Han, ZHL Zhou, et al. TNF- Suppresses IFN- -Induced MHC Class II Expression in HT1080 Cells by Destabilizing Class II trans-Activator mRNA. J. Immunol., 1999; 163: 1435 - 1440.
37. DP King and PP Jones. Induction of Ia and H-2 antigens on a macrophage cell line by immune interferon. J. Immunol., 1983; 131: 315 - 318.
38. PM Stuart, A Zlotnik, et al. Induction of class I and class II MHC antigen expression on murine bone marrow-derived macrophages by IL-4 (B cell stimulatory factor 1). J. Immunol., 1988. 140: 1542 - 1547.
39. K Frei, H Lins, et al. Antigen presentation in the central nervous system. The inhibitory effect of IL-10 on MHC class II expression and production of cytokines depends on the inducing signals and the type of cell analyzed. J. Immunol., 1994. 152: 2720 - 2728.
40. YJ Lee, Y Han, et al. TGF-beta suppresses IFN-γinduction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression. J. Immunol., 1997. 158: 2065 - 2075.
41. YS Dong, LP Tang, et al. The Smad3 Protein Is Involved in TGF- Inhibition of Class II Transactivator and Class II MHC Expression. J. Immunol., 2001. 167: 311 - 319.
42. MA Meraz, JM White, et al. Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell, 1996. 84:431.
43. U Boehm, T Klamp, et al. Cellular responses to interferon-gamma. Annu Rev Immunol, 1997; 15: 749-95.
44. JC Marine, DJ Topham, et al. SOCS1 deficiency causes a lymphocyte dependent perinatal lethality. Cell, 1999. 98:609.
45. JC Marine, C McKay, et al. SOCS3 is essential in the regulation of fetal livererythropoiesis. Cell, 1999. 98:617.
46. D Metcalf, CJ Greenhalgh, et al. Gigantism in mice lacking suppressor of cytokine signalling-2. Nature, 2000. 405:1069.
47. T Naka, T Matsumoto, et al. Accelerated apoptosis of lymphocytes by augmented induction of Bax in SSI-1 (STAT-induced STAT inhibitor-1) deficient mice. Proc. Natl. Acad. Sci, 1998. 95:15577.
48. DL Krebs and DJ Hilton. SOCS: physiological suppressors of cytokine signaling. J. Cell Sci, 2000. 113:2813.
49. WS Alexander, R Starr, et al. SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell, 1999; 98(5): 597-608.
50. TA Endo, M Masuhara, et al. A new protein containing an SH2 domain that inhibits JAK kinases. Nature, 1997. 387:921.
51. T Naka, M Narazaki, et al. Structure and function of a new STAT-induced STAT inhibitor. Nature, 1997. 387:924.
52. M Narazaki, M Fujimoto, et al. Three distinct domains of SSI-1/SOCS-1/JAB protein are required for its suppression of interleukin 6 signaling. Proc. Natl. Acad. Sci, 1998. 95:13130.
53. SE Nicholson, TA Willson, et al. Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL-6 signal transduction. EMBO J, 1999. 18:375.
54. H Yasukawa, H Misawa, et al. The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. EMBO J, 1999. 18:1309.
55. S Hiroshi, Y Hideo, et al. A Janus Kinase Inhibitor, JAB, Is an Interferon--Inducible Gene and Confers Resistance to Interferons. Blood, 1998; 92: 1668 -1676.
56. R Starr, D Metcalf, et al. Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1. Proc. Natl. Acad. Sci, 1998. 95:14395.
57. MM Song and K Shuai. The Suppressor of Cytokine Signaling (SOCS) 1 and SOCS3 but Not SOCS2 Proteins Inhibit Interferon-mediated Antiviral and Antiproliferative Activities. J. Biol. Chem., 1998; 273: 35056.
58. S Ilangumaran, D Finan, et al. A Positive Regulatory Role for Suppressor of Cytokine Signaling 1 in IFN- -Induced MHC Class II Expression in Fibroblasts. J. Immunol., 2002; 169: 5010 - 5020.
59. CV Ramana, MP Gil, et al. Stat1-independent regulation of gene expression in response to IFN- . PNAS, 2001; 98: 6674 - 6679.
60. NS Trede, RS Geha, et al. Transcriptional activation of IL-1 beta and tumor necrosis factor-alpha genes by MHC class II ligands. J. Immunol., 1991; 146: 2310 - 2315.
61. L Lei, J Altstaedt, et al. Induction of interleukin-8 in human neutrophils after MHC class II cross-linking with superantigens. J. Leukoc. Biol., 2001; 70: 80.
62. IL Yoshie, JF Piskurich, et al. Reduced IL-4-, Lipopolysaccharide-, and IFN--Induced MHC Class II Expression in Mice Lacking Class II Transactivator Due to Targeted Deletion of the GTP-Binding Domain. J. Immuno, 1999, 163: 2425-2431.
63. W Rohn, LP Tang, et al. IL-1? Inhibits IFN- -Induced Class II MHC Expression by Suppressing Transcription of the Class II Transactivator Gene. J. Immunol., 1999; 162: 886 - 896.
64. TJ Sisk, T Gourley, et al. MHC Class II Transactivator Inhibits IL-4 Gene Transcription by Competing with NF-AT to Bind the Coactivator CREBBinding Protein (CBP)/p300. J. Immunol., 2000; 165: 2511 - 2517.
65. B Seddon and D Mason. Effects of cytokines and glucocorticoids on endogenous class II MHC antigen expression by activated rat CD4+ T cells. Mature CD4+CD8–thymocytes are phenotypically heterogeneous on activation. Int. Immunol., 1996; 8: 1185 - 1193.
66. RW Satola, SH Sanchez, et al. Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DR promoter binding protein, RF-X. Cell, 1988; 53, 897-906.
67. V Steimle, B Durand, et al. A novel DNA-binding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome). Genes & Dev., 1995; 9: 1021 - 1032.
68. EL Roy, MM Annick, et al. Escape of Human Cytomegalovirus from HLA-DR-Restricted CD4+ T-Cell Response Is Mediated by Repression of Gamma Interferon-Induced Class II Transactivator Expression. J. Virol., 1999; 73: 6582 - 6589.
69. GM Zhong, T Fan, et al. Chlamydia Inhibits Interferon–inducible Major Histocompatibility Complex Class II Expression by Degradation of Upstream Stimulatory Factor 1. J. Exp. Med., 1999; 189: 1931 - 1938.
70. GM Zhong, Li Liu, et al. Degradation of Transcription Factor Rfx5 during the Inhibition of Both Constitutive and Interferon–Inducible Major Histocompatibility Complex Class I Expression in Chlamydia-Infected Cells. J. Exp. Med., 2000; 191: 1525 - 1534.
71. X Zhu, S Pattenden, et al. pRB is required for interferon-gamma-induction of the MHC class II abeta gene. Oncogene, 1999; 18(35): 4940-7.
72. FE Borras, J Lloberas, et al. Repression of I-A gene expression by the transcription factor PU.1. J. Biol. Chem. 1995. 270:24385.
73. D. Choubey, SJ Li, et al. Inhibition of E2F-mediated transcription by p202. EMBO J, 1996. 15:5668.
74. W Min, S Ghosh, et al. The interferon-inducible p202 protein as a modulator of transcription: inhibition of NF-kappa B, c-Fos, and c-Jun activities. Mol. Cell. Biol., 1996; 16: 359 - 368.
75. C Hengstenberg, G Hufnagel, et al. De novo expression of MHC class I and class II antigens on endomyocardial biopsies from patients with inflammatory heart disease and rejection following heart transplantation. Eur Heart J, 1993.14:758-763.
76. CD Preval, MR Hadam, et al. Regulation of genes for HLA class 11 antigens in cell lines from patients isith severe combined iinmunodeficiency. N. EngI. J. Med. 1988. 318, 1295-1300
77. E Le, HQ Zhang, et al. CIITA Transformation Rescues the Apoptotic Function of MHC Class II in Melanoma Cells. Anticancer Res, 2005; 25: 3889 - 3892.
78. S Redpath, A Angulo, et al. Murine Cytomegalovirus Infection Down-Regulates MHC Class II Expression on Macrophages by Induction of IL-10. J. Immunol., 1999; 162: 6701 - 6707.
79. CK Baumgartner, A Ferrante. et al. Peptide-MHCclass II complex stability governs CD4 T cell clonal selection. J. Immuno. 2010.184:573-581.