乙肝DNA疫苗联合佐剂的免疫效果评价及抗H7N9流感病毒新策略的研究
|
摘要
感染性疾病一直严重威胁着人类的健康和公共卫生的安全,已知60%以上的感染性疾病都是由病毒感染所引起的,而我国是乙肝重灾区,将近9.3%的人口是乙肝病毒携带者,每年有近20万人死于HBV感染相关的疾病。2013年3月突如其来的H7N9禽流感病毒已造成超过419人感染,其中约127人死亡,严重威胁着人们的生命安全和社会的安定。但是目前我们对病毒感染性疾病的预防和治疗尚缺乏有效的应对办法,因此研发安全有效的防治措施具有非常重要的意义。
由于DNA疫苗可以同时激活体液免疫和细胞免疫反应,因此被广泛应用于慢性乙肝等病毒感染性疾病的治疗,但在临床研究过程中发现DNA疫苗在大动物和人体内引起的免疫反应相对较弱。本实验室之前的研究发现临床上正在应用的两种小分子药物：西咪替丁和吡喹酮可以通过不同的方式增强乙肝DNA疫苗的治疗效果,本研究主要探讨西咪替丁联合吡喹酮是否可以产生协同效果进一步增强乙肝DNA疫苗的治疗效果。结果显示,西咪替丁联合吡喹酮作为乙肝DNA疫苗的佐剂可以显著降低体内CD4+CD25+Foxp3+调节性T细胞的数量和功能,从而增强乙肝DNA疫苗所诱导的抗原特异性CD8+T细胞的杀伤功能,进一步研究发现CD8+T细胞主要通过分泌IFN-y和IL-17A来发挥其杀伤作用,在HBsAg转基因小鼠模型中进一步证明了其治疗效果。鉴于这两种药物的既往临床安全性,有望作为乙肝DNA疫苗的候选佐剂。
IL-17是一种主要由Th17细胞分泌的新型细胞因子,被认为是连接固有免疫和适应性免疫反应的桥梁,而且在多种自主免疫性疾病(如银屑病、炎症性肠炎、多发性硬化症和类风湿性关节炎等)的发病过程中起到非常重要的作用。之前研究发现如果体内的IL-17A缺失后,小鼠对流感病毒的易感性明显增强,伴随着小鼠的体重和存活率下降,表明IL-17A在病毒感染过程中具有非常重要的作用。本研究通过检测不同流感病毒感染后患者血清中各种细胞因子的变化水平,我们发现血清中IL-17A的浓度越高,流感患者的病情相对较轻,预示着IL-17A可能参与到流感病毒感染的过程中并起到保护性的效果。在小鼠H7N9流感病毒的攻毒模型基础上,我们进一步证明IL-17A可以促进体内细胞因子IFN-γ的表达,从而抑制流感病毒的复制,降低肺部的病毒载量,增强小鼠抵抗H7N9禽流感病毒感染的能力。而且IL-17A在体外同样能够促进人外周血中的CD8+T细胞分泌IFN-γ的能力。本研究结果为研发基于IL-17A的新型抗H7N9禽流感病毒感染策略提供了新思路。
Infectious diseases continue to be the most serious threat to the public health. In fact, over sixty percentages of infectious diseases are caused by viral infections and hepatitis B are the highest incidence of infectious diseases in China. At present, there are over nine percentages of the population are infected with HBV and over200,000people died from HBV-related diseases each year. Since March2013, we had confirmed over419cases infected with newly-emerged H7N9avian influenza virus, with127deads. The high mortality rates and pandemic potentials threaten the social security and people's health. However, there are still no preferred preventions and treatment against viral infections. Therefore, investigations on developing novel therapeutic strategies have great significant for the prevention and control of viral infectious diseases.
DNA vaccine has a great potential to be used for the treatment of chronic HBV infection, owing to their advantage in stimulating both humoral immune responses and cellular immune responses. However, it drives significantly weaker immune responses in non-human primates and in humans compared with mice. Previously, we have shown that either cimetidine or praziquantel could enhance the therapeutic effects of HBV DNA vaccine through different pathways. The primary objectives of this study were to confirm whether cimetidine could synergize with praziquantel to enhance the immune response of HBV DNA vaccine. Here we show that combination of CIM and PZQ as adjuvants for a HBV DNA vaccine could not only significantly reduce the number and function of CD4+CD25+Foxp3+Tregs. In addition, the HBsAg-specific cytotoxic CD8+T cell was also elevated significantly, which is critical for the eradication of HBV infected cells. Further investigations demonstrated that the cytotoxic function of activated CD8+T cells was dependent on the expression of IFN-y and IL-17A. Using a HBsAg transgenic mouse model, the expression of HBsAg in the hepatic cells was also significantly reduced after immunized with pCD-S2in the presence of0.5%of CIM and0.25%of PZQ. Therefore, relative safety records for CIM and PZQ could make them as effective adjuvants for the development of therapeutic vaccines against chronic viral infections.
IL-17A is a newly-defined cytokine, mainly produced by Th17cells and considered to be a potent mediator to bridge innate and adaptive immune systems. Recently, IL-17A has been demonstrated to be involved in several autoimmune diseases, including psoriasis, rheumatoid arthritis, multiple sclerosis, and Crohn's diseases. Several investigations have reported the protective role of IL-17A in animal models of PR8influenza infection since neutralization of IL-17A in mice increases weight loss and reduces survival. This led us a great interest to investigate the protective role of IL-17A against H7N9virus infection and its mechanism. Here we analyzed the levels of different cytokines in the serum samples from patients infected with different influenza viruses and found that elevated serum levels of IL-17A are apparently associated with less severe disease in the H7N9-infected patients. Using an H7N9influenza virus infected mice model, we further confirmed that pre-administration with IL-17A could protect mice against lethal H7N9virus infection, the protective effects of IL-17A seems to be dependent on the secretion of IFN-y, an important host factor for viral clearance. In addition, IL-17A could also activate CD8+T cells isolated from healthy individuals' blood in vitro and upregulate the secretion of IFN-γ. Together, these findings reveal that IL-17A plays pivotal roles in hosts against lethal H7N9virus infection, provide us with new ideas on developing IL-17A based strategy to combat the emerging lethal Influenza viruses and give a new direction for developing anti-viral drugs.
由于DNA疫苗可以同时激活体液免疫和细胞免疫反应,因此被广泛应用于慢性乙肝等病毒感染性疾病的治疗,但在临床研究过程中发现DNA疫苗在大动物和人体内引起的免疫反应相对较弱。本实验室之前的研究发现临床上正在应用的两种小分子药物：西咪替丁和吡喹酮可以通过不同的方式增强乙肝DNA疫苗的治疗效果,本研究主要探讨西咪替丁联合吡喹酮是否可以产生协同效果进一步增强乙肝DNA疫苗的治疗效果。结果显示,西咪替丁联合吡喹酮作为乙肝DNA疫苗的佐剂可以显著降低体内CD4+CD25+Foxp3+调节性T细胞的数量和功能,从而增强乙肝DNA疫苗所诱导的抗原特异性CD8+T细胞的杀伤功能,进一步研究发现CD8+T细胞主要通过分泌IFN-y和IL-17A来发挥其杀伤作用,在HBsAg转基因小鼠模型中进一步证明了其治疗效果。鉴于这两种药物的既往临床安全性,有望作为乙肝DNA疫苗的候选佐剂。
IL-17是一种主要由Th17细胞分泌的新型细胞因子,被认为是连接固有免疫和适应性免疫反应的桥梁,而且在多种自主免疫性疾病(如银屑病、炎症性肠炎、多发性硬化症和类风湿性关节炎等)的发病过程中起到非常重要的作用。之前研究发现如果体内的IL-17A缺失后,小鼠对流感病毒的易感性明显增强,伴随着小鼠的体重和存活率下降,表明IL-17A在病毒感染过程中具有非常重要的作用。本研究通过检测不同流感病毒感染后患者血清中各种细胞因子的变化水平,我们发现血清中IL-17A的浓度越高,流感患者的病情相对较轻,预示着IL-17A可能参与到流感病毒感染的过程中并起到保护性的效果。在小鼠H7N9流感病毒的攻毒模型基础上,我们进一步证明IL-17A可以促进体内细胞因子IFN-γ的表达,从而抑制流感病毒的复制,降低肺部的病毒载量,增强小鼠抵抗H7N9禽流感病毒感染的能力。而且IL-17A在体外同样能够促进人外周血中的CD8+T细胞分泌IFN-γ的能力。本研究结果为研发基于IL-17A的新型抗H7N9禽流感病毒感染策略提供了新思路。
Infectious diseases continue to be the most serious threat to the public health. In fact, over sixty percentages of infectious diseases are caused by viral infections and hepatitis B are the highest incidence of infectious diseases in China. At present, there are over nine percentages of the population are infected with HBV and over200,000people died from HBV-related diseases each year. Since March2013, we had confirmed over419cases infected with newly-emerged H7N9avian influenza virus, with127deads. The high mortality rates and pandemic potentials threaten the social security and people's health. However, there are still no preferred preventions and treatment against viral infections. Therefore, investigations on developing novel therapeutic strategies have great significant for the prevention and control of viral infectious diseases.
DNA vaccine has a great potential to be used for the treatment of chronic HBV infection, owing to their advantage in stimulating both humoral immune responses and cellular immune responses. However, it drives significantly weaker immune responses in non-human primates and in humans compared with mice. Previously, we have shown that either cimetidine or praziquantel could enhance the therapeutic effects of HBV DNA vaccine through different pathways. The primary objectives of this study were to confirm whether cimetidine could synergize with praziquantel to enhance the immune response of HBV DNA vaccine. Here we show that combination of CIM and PZQ as adjuvants for a HBV DNA vaccine could not only significantly reduce the number and function of CD4+CD25+Foxp3+Tregs. In addition, the HBsAg-specific cytotoxic CD8+T cell was also elevated significantly, which is critical for the eradication of HBV infected cells. Further investigations demonstrated that the cytotoxic function of activated CD8+T cells was dependent on the expression of IFN-y and IL-17A. Using a HBsAg transgenic mouse model, the expression of HBsAg in the hepatic cells was also significantly reduced after immunized with pCD-S2in the presence of0.5%of CIM and0.25%of PZQ. Therefore, relative safety records for CIM and PZQ could make them as effective adjuvants for the development of therapeutic vaccines against chronic viral infections.
IL-17A is a newly-defined cytokine, mainly produced by Th17cells and considered to be a potent mediator to bridge innate and adaptive immune systems. Recently, IL-17A has been demonstrated to be involved in several autoimmune diseases, including psoriasis, rheumatoid arthritis, multiple sclerosis, and Crohn's diseases. Several investigations have reported the protective role of IL-17A in animal models of PR8influenza infection since neutralization of IL-17A in mice increases weight loss and reduces survival. This led us a great interest to investigate the protective role of IL-17A against H7N9virus infection and its mechanism. Here we analyzed the levels of different cytokines in the serum samples from patients infected with different influenza viruses and found that elevated serum levels of IL-17A are apparently associated with less severe disease in the H7N9-infected patients. Using an H7N9influenza virus infected mice model, we further confirmed that pre-administration with IL-17A could protect mice against lethal H7N9virus infection, the protective effects of IL-17A seems to be dependent on the secretion of IFN-y, an important host factor for viral clearance. In addition, IL-17A could also activate CD8+T cells isolated from healthy individuals' blood in vitro and upregulate the secretion of IFN-γ. Together, these findings reveal that IL-17A plays pivotal roles in hosts against lethal H7N9virus infection, provide us with new ideas on developing IL-17A based strategy to combat the emerging lethal Influenza viruses and give a new direction for developing anti-viral drugs.
引文
Aarvak, T., Chabaud, M., Miossec, P., and Natvig, J.B. (1999). IL-17 is produced by some proinflammatory Thl/ThO cells but not by Th2 cells. J. Immunol.162,1246-1251.
Aggarwal, S., and Gurney, A.L. (2002). IL-17:prototype member of an emerging cytokine family. J. Leukoc. Biol.71,1-8.
Akbar, S.M., Furukawa, S., Hasebe, A., Horiike, N., Michitaka, K., and Onji, M. (2004). Production and efficacy of a dendritic cell-based therapeutic vaccine for murine chronic hepatitis B virus carrierer. Int. J. Mol. Medicine 14,295-299.
Akdis, M., Blaser, K., and Akdis, C.A. (2005). T regulatory cells in allergy:novel concepts in the pathogenesis, prevention, and treatment of allergic diseases. J. Allergy Clin. Immunol.116,961-968; quiz 969.
Alexander, D.J. (2006). Avian influenza viruses and human health. Developments in biologicals 124,77-84.
Andrews, P. (1985). Praziquantel:mechanisms of anti-schistosomal activity. Pharmacol. Ther. 29,129-156.
Aronica, M.A., Mora, A.L., Mitchell, D.B., Finn, P.W., Johnson, J.E., Sheller, J.R., and Boothby, M.R. (1999). Preferential role for NF-kappa B/Rel signaling in the type 1 but not type 2 T cell-dependent immune response in vivo. J. Immunol.163,5116-5124.
Aune, T.M., Penix, L.A., Rincon, M.R., and Flavell, R.A. (1997). Differential transcription directed by discrete gamma interferon promoter elements in naive and memory (effector) CD4 T cells and CD8 T cells. Mol. and cell. Biol.17,199-208.
Awane, M., Andres, P.G., Li, D.J., and Reinecker, H.C. (1999). NF-kappa B-inducing kinase is a common mediator of IL-17-, TNF-alpha-, and IL-1 beta-induced chemokine promoter activation in intestinal epithelial cells. J. Immunol.162,5337-5344.
Banks, J., Speidel, E.C., McCauley, J.W., and Alexander, D.J. (2000). Phylogenetic analysis of H7 haemagglutinin subtype influenza A viruses. Arch. Virol.145,1047-1058.
Barth, H., Klein, R., Berg, P.A., Wiedenmann, B., Hopf, U., and Berg, T. (2001). Induction of T helper cell type 1 response and elimination of HBeAg during treatment with IL-12 in a patient with therapy-refractory chronic hepatitis B. Hepato-gastroenterology 48,553-555.
Beck, J., and Nassal, M. (2007). Hepatitis B virus replication. World J. Gastroenterol.13,48-64.
Belz, G.T., Smith, C.M., Eichner, D., Shortman, K., Karupiah, G., Carbone, F.R., and Heath, W.R. (2004). Cutting edge:conventional CD8 alpha+ dendritic cells are generally involved in priming CTL immunity to viruses. J. Immunol.172,1996-2000.
Beriou, G., Costantino, C.M., Ashley, C.W., Yang, L., Kuchroo, V.K., Baecher-Allan, C., and Hafler, D.A. (2009). IL-17-producing human peripheral regulatory T cells retain suppressive function. Blood 113, 4240-4249.
Bermejo-Martin, J.F., Ortiz de Lejarazu, R., Pumarola, T., Rello, J., Almansa, R., Ramirez, P., Martin-Loeches, I., Varillas, D., Gallegos, M.C., Seron, C., et al. (2009). Thl and Thl7 hypercytokinemia as early host response signature in severe pandemic influenza. Crit. Care 13, R201.
Bermejo, D.A., Jackson, S.W., Gorosito-Serran, M., Acosta-Rodriguez, E.V., Amezcua-Vesely, M.C., Sather, B.D., Singh, A.K., Khim, S., Mucci, J., Liggitt, D., et al. (2013). Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORgammat and Ahr that leads to IL-17 production by activated B cells. Nat. Immunol.14,514-522.
Biermer, M., Puro, R., and Schneider, R.J. (2003). Tumor necrosis factor alpha inhibition of hepatitis B virus replication involves disruption of capsid Integrity through activation of NF-kappaB. J. Virol.77, 4033-4042.
Blonska, M., and Lin, X. (2009). CARMA1-mediated NF-kappaB and JNK activation in lymphocytes. Immunol. Rev.228,199-211.
Boehme, K.W., and Compton, T. (2004). Innate sensing of viruses by toll-like receptors. J. Virol.78, 7867-7873.
Boettler, T., Spangenberg, H.C., Neumann-Haefelin, C., Panther, E., Urbani, S., Ferrari, C., Blum, H.E., von Weizsacker, F., and Thimme, R. (2005). T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection. J. Virol.79, 7860-7867.
Brackett, C., Maier, P., Ramsey, K., and Gollnick, S. (2009). Photodynamic Therapy Elicited Adaptive Immunity is Critically Dependent on IL-17 Bioactivity. J. Immunol.182,41.56-.
Brucklacher-Waldert, V, Stuerner, K., Kolster, M., Wolthausen, J., and Tolosa, E. (2009). Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis. Brain 132,3329-3341.
Campbell, P.M., Pimm, J., Ramassar, V, and Halloran, P.F. (1996). Identification of a calcium-inducible, cyclosporine sensitive element in the IFN-gamma promoter that is a potential NFAT binding site. Transplantation 61,933-939.
Cappello, P., Triebel, F., Iezzi, M., Caorsi, C., Quaglino, E., Lollini, P.L., Amici, A., Di Carlo, E., Musiani, P., Giovarelli, M., et al. (2003). LAG-3 enables DNA vaccination to persistently prevent mammary carcinogenesis in HER-2/neu transgenic BALB/c mice. Cancer Res.63,2518-2525.
Carey, I., D'Antiga, L., Bansal, S., Longhi, M.S., Ma, Y., Mesa, I.R., Mieli-Vergani, G., and Vergani, D. (2011). Immune and viral profile from tolerance to hepatitis B surface antigen clearance:a longitudinal study of vertically hepatitis B virus-infected children on combined therapy. J. Virol.85,2416-2428.
Chan, C.Y., Lee, S.D., and Lo, K.J. (2004). Legend of hepatitis B vaccination:the Taiwan experience. J. Gastroenterol. Hepatol.19,121-126.
Chan, H.L., Tang, J.L., Tam, W., and Sung, J.J. (2001). The efficacy of thymosin in the treatment of chronic hepatitis B virus infection:a meta-analysis. Aliment. Pharmacol. Ther.15,1899-1905.
Chang, J.J., Wightman, F., Bartholomeusz, A., Ayres, A., Kent, S.J., Sasadeusz, J., and Lewin, S.R. (2005). Reduced hepatitis B virus (HBV)-specific CD4+ T-cell responses in human immunodeficiency virus type 1-HBV-coinfected individuals receiving HBV-active antiretroviral therapy. J. Virol.79,3038-3051.
Chang, S.H., Park, H., and Dong, C. (2006). Actl adaptor protein is an immediate and essential signaling component of interleukin-17 receptor. J. Biol. Chem.281,35603-35607.
Chen, X., Zhang, W., Gao, W., Zou, Q., Feng, C., Liu, H., Zhou, C., Zhang, Y., and Wang, B. (2012). Hemokinin-1 as an adjuvant molecule enhancing humoral and memory responses to HBsAg DNA vaccination. Viral immunol.25,289-296.
Cheung, C.Y., Poon, L.L., Lau, A.S., Luk, W., Lau, Y.L., Shortridge, K.F., Gordon, S., Guan, Y., and Peiris, J.S. (2002). Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses:a mechanism for the unusual severity of human disease? Lancet 360,1831-1837.
Chisari, F.V., and Ferrari, C. (1995). Hepatitis B virus immunopathogenesis. Annu. Rev. Immunol.13,29-60.
Chow, Y.H., Chiang, B.L., Lee, Y.L., Chi, W.K., Lin, W.C., Chen, Y.T., and Tao, M.H. (1998). Development of Thl and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genes. J. Immunol.160,1320-1329.
Chow, Y.H., Huang, W.L., Chi, W.K., Chu, YD., and Tao, M.H. (1997). Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis B surface antigen and interleukin-2. J. Virol.71, 169-178.
Chowell, G., Bertozzi, S.M., Colchero, M.A., Lopez-Gatell, H., Alpuche-Aranda, C., Hernandez, M., and Miller, M.A. (2009). Severe respiratory disease concurrent with the circulation of H1N1 influenza. N. Engl. J. Med.361,674-679.
Crowe, S.R., Turner, S.J., Miller, S.C., Roberts, A.D., Rappolo, R.A., Doherty, P.C., Ely, K.H., and Woodland, D.L. (2003). Differential antigen presentation regulates the changing patterns of CD8+ T cell immunodominance in primary and secondary influenza virus infections. J. Exp. Med.198,399-410.
Cua, D.J., and Tato, C.M. (2010). Innate IL-17-producing cells:the sentinels of the immune system. Nat. Rev. Immunol.10,479-489.
Davis, H.L., McCluskie, M.J., Gerin, J.L., and Purcell, R.H. (1996). DNA vaccine for hepatitis B:evidence for immunogenicity in chimpanzees and comparison with other vaccines. Proc. Natl. Acad. Sci. U. S. A. 93,7213-7218.
de Jong, M.D., Tran, T.T., Truong, H.K., Vo, M.H., Smith, GJ., Nguyen, V.C., Bach, V.C., Phan, T.Q., Do, Q.H., Guan, Y., et al. (2005). Oseltamivir resistance during treatment of influenza A (H5N1) infection. N. Engl. J. Med.353,2667-2672.
Dong, C. (2008). Regulation and pro-inflammatory function of interleukin-17 family cytokines. Immunol. Rev.226,80-86.
Du, D.W., Jia, Z.S., Li, G.Y., and Zhou, Y.Y. (2003). HBV DNA vaccine with adjuvant cytokines induced specific immune responses against HBV infection. World J. Gastroenterol.9,108-111.
Du, X., Zheng, G., Jin, H., Kang, Y., Wang, J., Xiao, C., Zhang, S., Zhao, L., Chen, A., and Wang, B. (2007). The adjuvant effects of co-stimulatory molecules on cellular and memory responses to HBsAg DNA vaccination. J. Gene. Med.9,136-146.
Engelhardt, O.G., Sirma, H., Pandolfi, P.P., and Haller, O. (2004). Mxl GTPase accumulates in distinct nuclear domains and inhibits influenza A virus in cells that lack promyelocytic leukaemia protein nuclear bodies. J. Gen. Virol.85,2315-2326.
Ferrari, C., Bertoletti, A., Penna, A., Cavalli, A., Valli, A., Missale, G, Pilli, M., Fowler, P., Giuberti, T., Chisari, F.V., et al. (1991). Identification of immunodominant T cell epitopes of the hepatitis B virus nucleocapsid antigen. J. Clin. Invest.88,214-222.
Fisman, D.N., Savage, R., Gubbay, J., Achonu, C., Akwar, H., Farrell, D.J., Crowcroft, N.S., and Jackson, P. (2009). Older age and a reduced likelihood of 2009 H1N1 virus infection. N. Engl. J. Med.361, 2000-2001.
Furuichi, Y, Tokuyama, H., Ueha, S., Kurachi, M., Moriyasu, F., and Kakimi, K. (2005). Depletion of CD25+CD4+T cells (Tregs) enhances the HBV-specific CD8+ T cell response primed by DNA immunization. World J. Gastroenterol.11,3772-3777.
Gaffen, S.L. (2009). Structure and signalling in the IL-17 receptor family. Nat. Rev. Immunol.9,556-567.
Ganem, D., and Prince, A.M. (2004). Hepatitis B virus infection--natural history and clinical consequences. N. Engl. J. Med.350,1118-1129.
Ganguly, S., Liu, J., Pillai, V.B., Mittler, R.S., and Amara, R.R. (2010). Adjuvantive effects of anti-4-1BB agonist Ab and 4-1BBL DNA for a HIV-1 Gag DNA vaccine:different effects on cellular and humoral immunity. Vaccine 28,1300-1309.
Gao, R., Cao, B., Hu, Y., Feng, Z., Wang, D., Hu, W., Chen, J., Jie, Z., Qiu, H., Xu, K., et al. (2013). Human infection with a novel avian-origin influenza A (H7N9) virus. N. Engl. J. Med.368,1888-1897.
Garcia-Sastre, A., Egorov, A., Matassov, D., Brandt, S., Levy, D.E., Durbin, J.E., Palese, P., and Muster, T. (1998). Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252, 324-330.
Geng, S., Zhong, Y., Wang, S., Liu, H., Zou, Q., Xie, X., Li, C., Yu, Q., He, Z., and Wang, B. (2012). Amiloride enhances antigen specific CTL by faciliting HBV DNA vaccine entry into cells. PLoS One 7, e33015.
Ghoreschi, K., Laurence, A., Yang, X.P., Tato, C.M., McGeachy, M.J., Konkel, J.E., Ramos, H.L., Wei, L., Davidson, T.S., Bouladoux, N., et al. (2010). Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature 467,961-971.
Goubau, D., Deddouche, S., and Reis e Sousa, C. (2013). Cytosolic sensing of viruses. Immunity 38, 855-869.
Grabbe, S., and Schwarz, T. (1998). Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity. Immunol. Today 19,37-44.
Guidotti, L.G, Ishikawa, T., Hobbs, M.V., Matzke, B., Schreiber, R., and Chisari, F.V. (1996). Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 4,25-36.
Guidotti, L.G., Morris, A., Mendez, H., Koch, R., Silverman, R.H., Williams, B.R., and Chisari, F.V. (2002). Interferon-regulated pathways that control hepatitis B virus replication in transgenic mice. J. Virol.76, 2617-2621.
Guidotti, L.G, Rochford, R., Chung, J., Shapiro, M., Purcell, R., and Chisari, F.V. (1999). Viral clearance without destruction of infected cells during acute HBV infection. Science 284,825-829.
Harrington, L.E., Hatton, R.D., Mangan, P.R., Turner, H., Murphy, T.L., Murphy, K.M., and Weaver, C.T. (2005). Interleukin 17-producing CD4+effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat. Immunol.6,1123-1132.
Hay, A.J., and Hayden, F.G (2013). Oseltamivir resistance during treatment of H7N9 infection. Lancet 381, 2230-2232.
Heathcote, J., McHutchison, J., Lee, S., Tong, M., Benner, K., Minuk, G, Wright, T., Fikes, J., Livingston, B., Sette, A., et al. (1999). A pilot study of the CY-1899 T-cell vaccine in subjects chronically infected with hepatitis B virus. The CY1899 T Cell Vaccine Study Group. Hepatology 30,531-536.
Huang, C.H., Peng, S., He, L., Tsai, Y.C., Boyd, D.A., Hansen, T.H., Wu, T.C., and Hung, C.F. (2005). Cancer immunotherapy using a DNA vaccine encoding a single-chain trimer of MHC class I linked to an HPV-16 E6 immunodominant CTL epitope. Gene Ther.12,1180-1186.
Ishigame, H., Kakuta, S., Nagai, T., Kadoki, M., Nambu, A., Komiyama, Y., Fujikado, N., Tanahashi, Y, Akitsu, A., Kotaki, H., et al. (2009). Differential roles of interleukin-17A and-17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30,108-119.
Isogawa, M., Robek, M.D., Furuichi, Y, and Chisari, F.V. (2005). Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J. Virol.79,7269-7272.
Itoh, Y, Shinya, K., Kiso, M., Watanabe, T., Sakoda, Y., Hatta, M., Muramoto, Y, Tamura, D., Sakai-Tagawa, Y, Noda, T., et al. (2009). In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 460,1021-1025.
Iwasaki, A. (2012). A virological view of innate immune recognition. Annu. Rev. Microbiol.66,177-196.
Jafri, H.S., Chavez-Bueno, S., Mejias, A., Gomez, A.M., Rios, A.M., Nassi, S.S., Yusuf, M., Kapur, P., Hardy, R.D., Hatfield, J., et al. (2004). Respiratory Syncytial Virus Induces Pneumonia, Cytokine Response, Airway Obstruction, and Chronic Inflammatory Infiltrates Associated with Long-Term Airway Hyperresponsiveness in Mice. J. Infect. Dis.189,1856-1865.
Jelley-Gibbs, D.M., Brown, D.M., Dibble, J.P., Haynes, L., Eaton, S.M., and Swain, S.L. (2005). Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation. J. Exp. Med.202, 697-706.
Johansson, B.E., Bucher, D.J., and Kilbourne, E.D. (1989). Purified influenza virus hemagglutinin and neuraminidase are equivalent in stimulation of antibody response but induce contrasting types of immunity to infection. J. Virol.63,1239-1246.
Kakimi, K., Guidotti, L.G, Koezuka, Y, and Chisari, F.V. (2000). Natural killer T cell activation inhibits hepatitis B virus replication in vivo. J. Exp. Med.192,921-930.
Kakimi, K., Isogawa, M., Chung, J., Sette, A., and Chisari, F.V. (2002). Immunogenicity and tolerogenicity of hepatitis B virus structural and nonstructural proteins:implications for immunotherapy of persistent viral infections. J. Virol.76,8609-8620.
Kim, S.J., Suh, D., Park, S.E., Park, J.S., Byun, H.M., Lee, C., Lee, S.Y., Kim, I., and Oh, Y.K. (2003). Enhanced immunogenicity of DNA fusion vaccine encoding secreted hepatitis B surface antigen and chemokine RANTES. Virology 314,84-91.
Kimura, K., Kakimi, K., Wieland, S., Guidotti, L.G., and Chisari, F.V. (2002a). Activated intrahepatic antigen-presenting cells inhibit hepatitis B virus replication in the liver of transgenic mice. J. Immunol. 169,5188-5195.
Kimura, K., Kakimi, K., Wieland, S., Guidotti, L.G, and Chisari, F.V. (2002b). Interleukin-18 inhibits hepatitis B virus replication in the livers of transgenic mice. J. Virol.76,10702-10707.
Kimura, K., Kakimi, K., Wieland, S., Guidotti, L.G, and Chisari, F.V. (2002c). Interleukin-18 inhibits hepatitis B virus replication in the livers of transgenic mice. J. Virol.76,10702-10707.
Kinter, A.L., Hennessey, M., Bell, A., Kern, S., Lin, Y., Daucher, M., Planta, M., McGlaughlin, M., Jackson, R., Ziegler, S.F., et al. (2004). CD25(+)CD4(+) regulatory T cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4(+) and CD8(+) HIV-specific T cell immune responses in vitro and are associated with favorable clinical markers of disease status. J. Exp. Med.200, 331-343.
Kirkham, B.W., Kavanaugh, A., and Reich, K. (2014). Interleukin-17A:a unique pathway in immune-mediated diseases:psoriasis, psoriatic arthritis and rheumatoid arthritis. Immunology 141, 133-142.
Kutzler, M.A., and Weiner, D.B. (2008). DNA vaccines:ready for prime time? Nat. Rev. Genet.9,776-788.
Lambrecht, B.N., Kool, M., Willart, M.A., and Hammad, H. (2009). Mechanism of action of clinically approved adjuvants. Curr. Opin. Immunol.21,23-29.
Langrish, C.L., Chen, Y., Blumenschein, W.M., Mattson, J., Basham, B., Sedgwick, J.D., McClanahan, T., Kastelein, R.A., and Cua, D.J. (2005). IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med.201,233-240.
Lee, Y.K., Turner, H., Maynard, C.L., Oliver, J.R., Chen, D., Elson, C.O., and Weaver, C.T. (2009). Late developmental plasticity in the T helper 17 lineage. Immunity 30,92-107.
Legge, K.L., and Braciale, T.J. (2003). Accelerated migration of respiratory dendritic cells to the regional lymph nodes is limited to the early phase of pulmonary infection. Immunity 18,265-277.
Li, J., Qiu, S.J., She, W.M., Wang, F.P., Gao, H., Li, L., Tu, C.T., Wang, J.Y., Shen, X.Z., and Jiang, W. (2012). Significance of the balance between regulatory T (Treg) and T helper 17 (Th17) cells during hepatitis B virus related liver fibrosis. PLoS One 7, e39307.
Li, J., Wu, W., Peng, G, Chen, F., Bai, M., Zheng, M., and Chen, Z. (2010). HBcAg induces interleukin-10 production, inhibiting HBcAg-specific Th17 responses in chronic hepatitis B patients. Immunol. Cell. Biol.88,834-841.
Li, M.J., Lei, J.H., Wang, T., Lu, S.J., Guan, F., Liu, W.Q., and Li, Y.L. (2011). Cimetidine enhances the protective effect of GST DNA vaccine against Schistosoma japonicum. Exp. Parasitol.128,427-432.
Liang, M, Ma, S., Hu, X., Zhou, B., Zhang, J., Chen, J., Wang, Z., Sun, J., Zhu, X., Abbott, W., et al. (2011). Cellular immune responses in patients with hepatitis B surface antigen seroclearance induced by antiviral therapy. Virol. J.8,69.
Lindemann, M.J., Hu, Z., Benczik, M., Liu, K.D., and Gaffen, S.L. (2008). Differential regulation of the IL-17 receptor by gammac cytokines:inhibitory signaling by the phosphatidylinositol 3-kinase pathway. J. Biol. Chem.283,14100-14108.
Lindstrom, S.E., Cox, N.J., and Klimov, A. (2004). Genetic analysis of human H2N2 and early H3N2 influenza viruses,1957-1972:evidence for genetic divergence and multiple reassortment events. Virology 328,101-119.
Liu, L., Huang, D., Matsui, M., He, T.T., Hu, T., Demartino, J., Lu, B., Gerard, C, and Ransohoff, R.M. (2006). Severe disease, unaltered leukocyte migration, and reduced IFN-gamma production in CXCR3-/-mice with experimental autoimmune encephalomyelitis. J. Immunol.176,4399-4409.
Lock, C., Hermans, G., Pedotti, R., Brendolan, A., Schadt, E., Garren, H., Langer-Gould, A., Strober, S., Cannella, B., Allard, J., et al. (2002). Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med.8,500-508.
Lok, A.S. (2002). Chronic hepatitis B. N. Engl. J. Med.346,1682-1683.
Ma, R., Du, J.L., Huang, J., and Wu, C.Y. (2007). Additive effects of CpG ODN and R-848 as adjuvants on augmenting immune responses to HBsAg vaccination. Biochem. Biophys. Res. Commun.361,537-542.
MacGregor, R.R., Boyer, J.D., Ugen, K.E., Lacy, K.E., Gluckman, S.J., Bagarazzi, M.L., Chattergoon, M.A., Baine, Y., Higgins, T.J., Ciccarelli, R.B., et al. (1998). First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection:safety and host response. The J. Infect. Dis.178,92-100.
Maini, M.K., Boni, C., Lee, C.K., Larrubia, J.R., Reignat, S., Ogg, G.S., King, A.S., Herberg, J., Gilson, R., Alisa, A., et al. (2000). The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. J. Exp. Med.191,1269-1280.
Maini, M.K., Boni, C., Ogg, G.S., King, A.S., Reignat, S., Lee, C.K., Larrubia, J.R., Webster, G.J., McMichael, A.J., Ferrari, C., et al. (1999). Direct ex vivo analysis of hepatitis B virus-specific CD8(+) T cells associated with the control of infection. Gastroenterology 117,1386-1396.
Maitra, A., Shen, F., Hanel, W., Mossman, K., Tocker, J., Swart, D., and Gaffen, S.L. (2007). Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression. Proc. Natl. Acad. Sci. U. S. A.104,7506-7511.
Mancini, M., Hadchouel, M., Davis, H.L., Whalen, R.G., Tiollais, P., and Michel, M.L. (1996). DNA-mediated immunization in a transgenic mouse model of the hepatitis B surface antigen chronic carrier state. Proc. Natl. Acad. Sci. U. S. A.93,12496-12501.
Matusevicius, D., Kivisakk, P., He, B., Kostulas, N., Ozenci, V., Fredrikson, S., and Link, H. (1999). Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult. Scler.5,101-104.
McGeachy, M.J., Bak-Jensen, K.S., Chen, Y., Tato, C.M., Blumenschein, W., McClanahan, T., and Cua, D.J. (2007). TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat. Immunol.8,1390-1397.
Mejias, A., Chavez-Bueno, S., Rios, A.M., Saavedra-Lozano, J., Fonseca Aten, M., Hatfield, J., Kapur, P., Gomez, A.M., Jafri, H.S., and Ramilo, O. (2004). Anti-Respiratory Syncytial Virus (RSV) Neutralizing Antibody Decreases Lung Inflammation, Airway Obstruction, and Airway Hyperresponsiveness in a Murine RSV Model. Antimicrob. Agents Chemother.48,1811-1822.
Mizukoshi, E., Sidney, J., Livingston, B., Ghany, M., Hoofhagle, J.H., Sette, A., and Rehermann, B. (2004). Cellular immune responses to the hepatitis B virus polymerase. J. Immunol.173,5863-5871.
Morefield, G.L., Sokolovska, A., Jiang, D., HogenEsch, H., Robinson, J.P., and Hem, S.L. (2005). Role of aluminum-containing adjuvants in antigen internalization by dendritic cells in vitro. Vaccine 23, 1588-1595.
Morens, D.M., Folkers, G.K., and Fauci, A.S. (2004). The challenge of emerging and re-emerging infectious diseases. Nature 430,242-249.
Moscona, A. (2005). Oseltamivir resistance--disabling our influenza defenses. N. Engl. J. Med.353, 2633-2636.
Munks, M.W., Mourich, D.V., Mittler, R.S., Weinberg, A.D., and Hill, A.B. (2004).4-1BB and OX40 stimulation enhance CD8 and CD4 T-cell responses to a DNA prime, poxvirus boost vaccine. Immunology 112,559-566.
Murray, J.M., Wieland, S.F., Purcell, R.H., and Chisari, F.V. (2005). Dynamics of hepatitis B virus clearance in chimpanzees. Proc. Natl. Acad. Sci. U. S. A.102,17780-17785.
O'Mahony, L., Akdis, M., and Akdis, C.A. (2011). Regulation of the immune response and inflammation by histamine and histamine receptors. J. Allergy Clin. Immunol.128,1153-1162.
O'Shea, J.J., and Paul, W.E. (2010). Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 327,1098-1102.
Ouyang, W., Kolls, J.K., and Zheng, Y. (2008). The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28,454-467.
Pan, C.Q., and Zhang, J.X. (2005). Natural History and Clinical Consequences of Hepatitis B Virus Infection. Int. J. Med. Sci.2,36-40.
Pancholi, P., Lee, D.H., Liu, Q., Tackney, C., Taylor, P., Perkus, M., Andrus, L., Brotman, B., and Prince, A.M. (2001). DNA prime/canarypox boost-based immunotherapy of chronic hepatitis B virus infection in a chimpanzee. Hepatology 33,448-454.
Papatheodoridis, G.V., Dimou, E., and Papadimitropoulos, V. (2002). Nucleoside analogues for chronic hepatitis B:antiviral efficacy and viral resistance. Am. J. Gastroenterol.97,1618-1628.
Park, H., Li, Z., Yang, X.O., Chang, S.H., Nurieva, R., Wang, Y.H., Wang, Y, Hood, L., Zhu, Z., Tian, Q., et al. (2005). A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol.6,1133-1141.
Partridge, J., and Kieny, M.P. (2013). Global production capacity of seasonal influenza vaccine in 2011. Vaccine 31,728-731.
Pearce, E.L., Mullen, A.C., Martins, GA., Krawczyk, C.M., Hutchins, A.S., Zediak, V.P., Banica, M., DiCioccio, C.B., Gross, D.A., Mao, C.A., et al. (2003). Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science 302,1041-1043.
Penix, L.A., Sweetser, M.T., Weaver, W.M., Hoeffler, J.P., Kerppola, T.K., and Wilson, C.B. (1996). The proximal regulatory element of the interferon-gamma promoter mediates selective expression in T cells. J. Biol. Chem.271,31964-31972.
Penna, A., Artini, M., Cavalli, A., Levrero, M., Bertoletti, A., Pilli, M., Chisari, F.V., Rehermann, B., Del Prete, G., Fiaccadori, F., et al. (1996). Long-lasting memory T cell responses following self-limited acute hepatitis B. J. Clin. Invest.98,1185-1194.
Penna, A., Del Prete, G., Cavalli, A., Bertoletti, A., D'Elios, M.M., Sorrentino, R., D'Amato, M., Boni, C., Pilli, M., Fiaccadori, F., et al. (1997). Predominant T-helper 1 cytokine profile of hepatitis B virus nucleocapsid-specific T cells in acute self-limited hepatitis B. Hepatology 25,1022-1027.
Pignatelli, M., Waters, J., Lever, A., Iwarson, S., Gerety, R., and Thomas, H.C. (1987). Cytotoxic T-Cell Responses to the Nucleocapsid Proteins of Hbv in Chronic Hepatitis-Evidence That Antibody Modulation May Cause Protracted Infection. J. Hepatol.4,15-21.
Pol, S., Driss, F., Michel, M.L., Nalpas, B., Berthelot, P., and Brechot, C. (1994). Specific vaccine therapy in chronic hepatitis B infection. Lancet 344,342.
Reed, S.G., Bertholet, S., Coler, R.N., and Friede, M. (2009). New horizons in adjuvants for vaccine development. Trends Immunol.30,23-32.
Rehermann, B., Fowler, P., Sidney, J., Person, J., Redeker, A., Brown, M., Moss, B., Sette, A., and Chisari, F.V. (1995). The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis. J. Exp. Med.181,1047-1058.
Rehermann, B., Lau, D., Hoofnagle, J.H., and Chisari, F.V. (1996). Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection. J. Clin. Invest.97,1655-1665.
Rehermann, B., and Nascimbeni, M. (2005). Immunology of hepatitis B virus and hepatitis C virus infection. Nat. Rev. Immunol.5,215-229.
Reignat, S., Webster, G.J., Brown, D., Ogg, GS., King, A., Seneviratne, S.L., Dusheiko, G, Williams, R., Maini, M.K., and Bertoletti, A. (2002). Escaping high viral load exhaustion:CD8 cells with altered tetramer binding in chronic hepatitis B virus infection. J. Exp. Med.195,1089-1101.
Roth, E., and Pircher, H. (2004). IFN-gamma promotes Fas ligand- and perforin-mediated liver cell destruction by cytotoxic CD8 T cells. J. Immunol.172,1588-1594.
Ruddy, M.J., Wong, G.C., Liu, X.K., Yamamoto, H., Kasayama, S., Kirkwood, K.L., and Gaffen, S.L. (2004). Functional cooperation between interleukin-17 and tumor necrosis factor-alpha is mediated by CCAAT/enhancer-binding protein family members. J. Biol. Chem.279,2559-2567.
Sasaki, M., Foccacia, R., and de Messias-Reason, I.J. (2003). Efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant for hepatitis B virus in patients with HIV infection. Vaccine 21,4545-4549.
Schwandner, R., Yamaguchi, K., and Cao, Z. (2000). Requirement of tumor necrosis factor receptor-associated factor (TRAF)6 in interleukin 17 signal transduction. J. Exp. Med.191,1233-1240.
Sealy, R., Surman, S., Hurwitz, J.L., and Coleclough, C. (2003). Antibody response to influenza infection of mice:different patterns for glycoprotein and nucleocapsid antigens. Immunology 108,431-439.
Shen, F., Ruddy, M.J., Plamondon, P., and Gaffen, S.L. (2005). Cytokines link osteoblasts and inflammation: microarray analysis of interleukin-17- and TNF-alpha-induced genes in bone cells. J. Leukoc. Biol.77, 388-399.
Shi, T.D., Wu, Y.Z., Jia, Z.C., Zou, L.Y., and Zhou, W. (2004). Therapeutic polypeptides based on HBV core 18-27 epitope can induce CD8+ CTL-mediated cytotoxicity in HLA-A2+ human PBMCs. World J. Gastroenterol.10,1902-1906.
Sica, A., Dorman, L., Viggiano, V., Cippitelli, M., Ghosh, P., Rice, N., and Young, H.A. (1997). Interaction of NF-kappaB and NFAT with the interferon-gamma promoter. J. Biol. Chem.272,30412-30420.
Spanaus, K.S., Schlapbach, R., and Fontana, A. (1998). TNF-alpha and IFN-gamma render microglia sensitive to Fas ligand-induced apoptosis by induction of Fas expression and down-regulation of Bcl-2 and Bcl-xL. European J. Immunol.28,4398-4408.
Sprengers, D., van der Molen, R.G., Kusters, J.G, Hansen, B., Niesters, H.G, Schalm, S.W., and Janssen, H.L. (2006). Different composition of intrahepatic lymphocytes in the immune-tolerance and immune-clearance phase of chronic hepatitis B. J. Med. Virol.78,561-568.
Stoop, J.N., van der Molen, R.G., Baan, C.C., van der Laan, L.J., Kuipers, E.J., Kusters, J.G., and Janssen, H.L. (2005). Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology 41,771-778.
Subbarao, K., and Joseph, T. (2007). Scientific barriers to developing vaccines against avian influenza viruses. Nat. Rev. Immunol.7,267-278.
Sweetser, M.T., Hoey, T., Sun, Y.L., Weaver, W.M., Price, GA., and Wilson, C.B. (1998). The roles of nuclear factor of activated T cells and ying-yang 1 in activation-induced expression of the interferon-gamma promoter in T cells. J. Biol. Chem.273,34775-34783.
Szabo, S.J., Kim, S.T., Costa, G.L., Zhang, X., Fathman, C.G., and Glimcher, L.H. (2000). A novel transcription factor, T-bet, directs Thl lineage commitment. Cell 100,655-669.
Szabo, S.J., Sullivan, B.M., Stemmann, C., Satoskar, A.R., Sleckman, B.P., and Glimcher, L.H. (2002). Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 295,338-342.
Tacket, C.O., Roy, M.J., Widera, G., Swain, W.F., Broome, S., and Edelman, R. (1999). Phase 1 safety and immune response studies of a DNA vaccine encoding hepatitis B surface antigen delivered by a gene delivery device. Vaccine 17,2826-2829.
Takatori, H., Kanno, Y., Watford, W.T., Tato, C.M., Weiss, G., Ivanov, Ⅱ, Littman, D.R., and O'Shea, J.J. (2009). Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J. Exp. Med.206, 35-41.
Tang, T.J., Kwekkeboom, J., Laman, J.D., Niesters, H.G., Zondervan, P.E., de Man, R.A., Schalm, S.W., and Janssen, H.L. (2003). The role of intrahepatic immune effector cells in inflammatory liver injury and viral control during chronic hepatitis B infection. J. Viral Hepat.10,159-167.
Tarr, P.E., Lin, R., Mueller, E.A., Kovarik, J.M., Guillaume, M., and Jones, T.C. (1996). Evaluation of tolerability and antibody response after recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and a single dose of recombinant hepatitis B vaccine. Vaccine 14,1199-1204.
Thimme, R., Wieland, S., Steiger, C., Ghrayeb, J., Reimann, K.A., Purcell, R.H., and Chisari, F.V. (2003). CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J. Virol.77,68-76.
Townsend, M.J., Weinmann, A.S., Matsuda, J.L., Salomon, R., Farnham, P.J., Biron, C.A., Gapin, L., and Glimcher, L.H. (2004). T-bet regulates the terminal maturation and homeostasis of NK and Valphal4i NKT cells. Immunity 20,477-494.
Tripp, R.A., Topham, D.J., Watson, S.R., and Doherty, P.C. (1997). Bone marrow can function as a lymphoid organ during a primary immune response under conditions of disrupted lymphocyte trafficking. J. Immunol.158,3716-3720.
Tumpey, T.M., Garcia-Sastre, A., Taubenberger, J.K., Palese, P., Swayne, D.E., Pantin-Jackwood, M.J., Schultz-Cherry, S., Solorzano, A., Van Rooijen, N., Katz, J.M., et al. (2005). Pathogenicity of influenza viruses with genes from the 1918 pandemic virus:functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice. J. Virol.79,14933-14944.
Turan, K., Mibayashi, M., Sugiyama, K., Saito, S., Numajiri, A., and Nagata, K. (2004). Nuclear MxA proteins form a complex with influenza virus NP and inhibit the transcription of the engineered influenza virus genome. Nucleic Acids Res.32,643-652.
van Zonneveld, M., Honkoop, P., Hansen, B.E., Niesters, H.G., Darwish Murad, S., de Man, R.A., Schalm, S.W., and Janssen, H.L. (2004). Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology 39,804-810.
Vignali, D.A., Collison, L.W., and Workman, C.J. (2008). How regulatory T cells work. Nat. Rev. Immunol. 8,523-532.
Wang, J., Su, B., Ding, Z., Du, X., and Wang, B. (2008). Cimetidine enhances immune response of HBV DNA vaccination via impairment of the regulatory function of regulatory T cells. Biochem. Biophys. Res. Commun.372,491-496.
Watanabe, K., Mwinzi, P.N., Black, C.L., Muok, E.M., Karanja, D.M., Secor, W.E., and Colley, D.G. (2007). T regulatory cell levels decrease in people infected with Schistosoma mansoni on effective treatment. Am. J. Trop. Med. Hyg.77,676-682.
Webster, GJ., Reignat, S., Maini, M.K., Whalley, S.A., Ogg, GS., King, A., Brown, D., Amlot, P.L., Williams, R., Vergani, D., et al. (2000). Incubation phase of acute hepatitis B in man:dynamic of cellular immune mechanisms. Hepatology 32,1117-1124.
Webster, R.G., Bean, W.J., Gorman, O.T., Chambers, T.M., and Kawaoka, Y. (1992). Evolution and ecology of influenza A viruses. Microbiol. Rev.56,152-179.
Wen, Y.M., Wu, X.H., Hu, D.C., Zhang, Q.P., and Guo, S.Q. (1995). Hepatitis B vaccine and anti-HBs complex as approach for vaccine therapy. Lancet 345,1575-1576.
Wherry, E.J., Blattman, J.N., Murali-Krishna, K., van der Most, R., and Ahmed, R. (2003). Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J. Virol.77,4911-4927.
Wieland, S.F., Guidotti, L.G, and Chisari, F.V. (2000). Intrahepatic induction of alpha/beta interferon eliminates viral RNA-containing capsids in hepatitis B virus transgenic mice. J. Virol.74,4165-4173.
Wong, D.K., Cheung, A.M., O'Rourke, K., Naylor, C.D., Detsky, A.S., and Heathcote, J. (1993). Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann. Intern. Med.119,312-323.
Workman, C.J., Szymczak-Workman, A.L., Collison, L.W., Pillai, M.R., and Vignali, D.A. (2009). The development and function of regulatory T cells. Cell. Mol. Life Sci.66,2603-2622.
Wu, B., Zou, Q., Hu, Y., and Wang, B. (2013). Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8(+) T cell responses against a HBV DNA vaccine in mice. Hum. Vaccin. Immunother.9.
Xu, D.Z., Huang, K.L., Zhao, K., Xu, L.F., Shi, N., Yuan, Z.H., and Wen, Y.M. (2005). Vaccination with recombinant HBsAg-HBIG complex in healthy adults. Vaccine 23,2658-2664.
Xu, D.Z., Zhao, K., Guo, L.M., Li, L.J., Xie, Q., Ren, H., Zhang, J.M., Xu, M., Wang, H.F., Huang, W.X., et al. (2008). A randomized controlled phase Ⅱb trial of antigen-antibody immunogenic complex therapeutic vaccine in chronic hepatitis B patients. PLoS One 3, e2565.
Yamazaki, S., Muta, T., Matsuo, S., and Takeshige, K. (2005). Stimulus-specific induction of a novel nuclear factor-kappaB regulator, IkappaB-zeta, via Toll/Interleukin-1 receptor is mediated by mRNA stabilization. J. Biol. Chem.280,1678-1687.
Yan, H., Zhong, G., Xu, G, He, W., Jing, Z., Gao, Z., Huang, Y, Qi, Y, Peng, B., Wang, H., et al. (2012). Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife 1, e00049.
Yao, Z., Fanslow, W.C., Seldin, M.F., Rousseau, A.M., Painter, S.L., Comeau, M.R., Cohen, J.I., and Spriggs, M.K. (1995). Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 3,811-821.
Ye, J., Su, X., Hsueh, E.C., Zhang, Y, Koenig, J.M., Hoft, D.F., and Peng, G. (2011). Human tumor-infiltrating Th17 cells have the capacity to differentiate into IFN-gamma+ and FOXP3+ T cells with potent suppressive function. European J. Immunol.41,936-951.
Yu, H., Cowling, B.J., Feng, L., Lau, E.H., Liao, Q., Tsang, T.K., Peng, Z., Wu, P., Liu, F., Fang, V.J, et al. (2013). Human infection with avian influenza A H7N9 virus:an assessment of clinical severity. Lancet 382,138-145.
Yu, J.J., and Gaffen, S.L. (2008). Interleukin-17:a novel inflammatory cytokine that bridges innate and adaptive immunity. Front, biosci.13,170-177.
Zhang, J.Y., Song, C.H., Shi, F., Zhang, Z., Fu, J.L., and Wang, F.S. (2010). Decreased ratio of Treg cells to Th17 cells correlates with HBV DNA suppression in chronic hepatitis B patients undergoing entecavir treatment. PLoS One 5, e13869.
Zhang, Q., Shi, J., Deng, G, Guo, J., Zeng, X., He, X., Kong, H., Gu, C., Li, X., Liu, J., et al. (2013). H7N9 influenza viruses are transmissible in ferrets by respiratory droplet. Science 341,410-414.
Zhang, W., Du, X., Zhao, G, Jin, H., Kang, Y., Xiao, C., Liu, M., and Wang, B. (2009). Levamisole is a potential facilitator for the activation of Thl responses of the subunit HBV vaccination. Vaccine 27, 4938-4946.
Zhang, X., Yu, C., Zhao, J., Fu, L., Yi, S., Liu, S., Yu, T., and Chen, W. (2007). Vaccination with a DNA vaccine based on human PSCA and HSP70 adjuvant enhances the antigen-specific CD8+ T-cell response and inhibits the PSCA+ tumors growth in mice. J. Gene. Med.9,715-726.
Zhu, Z., Yang, Y., Feng, Y, Shi, B., Chen, L., Zheng, Y, Tian, D., Song, Z., Xu, C., Qin, B., et al. (2013). Infection of inbred BALB/c and C57BL/6 and outbred Institute of Cancer Research mice with the emerging H7N9 avian influenza virus. Emerg. Microbes Infect.2, e50.
Zou, Q., Hu, Y, Xue, J., Fan, X., Jin, Y, Shi, X., Meng, D., Wang, X., Feng, C., Xie, X., et al. (2012). Use of praziquantel as an adjuvant enhances protection and Tc-17 responses to killed H5N1 virus vaccine in mice. PLoS One 7, e34865.
Zou, Q., Yao, X., Feng, J., Yin, Z., Flavell, R., Hu, Y, Zheng, G, Jin, J., Kang, Y, Wu, B., et al. (2011). Praziquantel facilitates IFN-gamma-producing CD8+ T cells (Tcl) and IL-17-producing CD8+ T cells (Tc17) responses to DNA vaccination in mice. PLoS One 6, e25525.
Zou, Q., Zhong, Y, Su, H., Kang, Y, Jin, J., Liu, Q., Geng, S., Zhao, G, and Wang, B. (2010). Enhancement of humoral and cellular responses to HBsAg DNA vaccination by immunization with praziquantel through inhibition TGF-beta/Smad2,3 signaling. Vaccine 28,2032-2038.
王晓军,张荣珍,胡苑笙,梁晓峰(2004).我国病毒性肝炎流行现状研究.疾病监测19,290-292.
杨富强,陈光明,饶桂荣,徐宇虹,赵勇刚,何晓嫱,孙希海,侯金林(2008). IL-2/IFN-γ融合蛋白基因质粒联合HBV DNA疫苗治疗HBV转基因小鼠效果评价.热带医学杂志,408-411.
Aggarwal, S., and Gurney, A.L. (2002). IL-17:prototype member of an emerging cytokine family. J. Leukoc. Biol.71,1-8.
Akbar, S.M., Furukawa, S., Hasebe, A., Horiike, N., Michitaka, K., and Onji, M. (2004). Production and efficacy of a dendritic cell-based therapeutic vaccine for murine chronic hepatitis B virus carrierer. Int. J. Mol. Medicine 14,295-299.
Akdis, M., Blaser, K., and Akdis, C.A. (2005). T regulatory cells in allergy:novel concepts in the pathogenesis, prevention, and treatment of allergic diseases. J. Allergy Clin. Immunol.116,961-968; quiz 969.
Alexander, D.J. (2006). Avian influenza viruses and human health. Developments in biologicals 124,77-84.
Andrews, P. (1985). Praziquantel:mechanisms of anti-schistosomal activity. Pharmacol. Ther. 29,129-156.
Aronica, M.A., Mora, A.L., Mitchell, D.B., Finn, P.W., Johnson, J.E., Sheller, J.R., and Boothby, M.R. (1999). Preferential role for NF-kappa B/Rel signaling in the type 1 but not type 2 T cell-dependent immune response in vivo. J. Immunol.163,5116-5124.
Aune, T.M., Penix, L.A., Rincon, M.R., and Flavell, R.A. (1997). Differential transcription directed by discrete gamma interferon promoter elements in naive and memory (effector) CD4 T cells and CD8 T cells. Mol. and cell. Biol.17,199-208.
Awane, M., Andres, P.G., Li, D.J., and Reinecker, H.C. (1999). NF-kappa B-inducing kinase is a common mediator of IL-17-, TNF-alpha-, and IL-1 beta-induced chemokine promoter activation in intestinal epithelial cells. J. Immunol.162,5337-5344.
Banks, J., Speidel, E.C., McCauley, J.W., and Alexander, D.J. (2000). Phylogenetic analysis of H7 haemagglutinin subtype influenza A viruses. Arch. Virol.145,1047-1058.
Barth, H., Klein, R., Berg, P.A., Wiedenmann, B., Hopf, U., and Berg, T. (2001). Induction of T helper cell type 1 response and elimination of HBeAg during treatment with IL-12 in a patient with therapy-refractory chronic hepatitis B. Hepato-gastroenterology 48,553-555.
Beck, J., and Nassal, M. (2007). Hepatitis B virus replication. World J. Gastroenterol.13,48-64.
Belz, G.T., Smith, C.M., Eichner, D., Shortman, K., Karupiah, G., Carbone, F.R., and Heath, W.R. (2004). Cutting edge:conventional CD8 alpha+ dendritic cells are generally involved in priming CTL immunity to viruses. J. Immunol.172,1996-2000.
Beriou, G., Costantino, C.M., Ashley, C.W., Yang, L., Kuchroo, V.K., Baecher-Allan, C., and Hafler, D.A. (2009). IL-17-producing human peripheral regulatory T cells retain suppressive function. Blood 113, 4240-4249.
Bermejo-Martin, J.F., Ortiz de Lejarazu, R., Pumarola, T., Rello, J., Almansa, R., Ramirez, P., Martin-Loeches, I., Varillas, D., Gallegos, M.C., Seron, C., et al. (2009). Thl and Thl7 hypercytokinemia as early host response signature in severe pandemic influenza. Crit. Care 13, R201.
Bermejo, D.A., Jackson, S.W., Gorosito-Serran, M., Acosta-Rodriguez, E.V., Amezcua-Vesely, M.C., Sather, B.D., Singh, A.K., Khim, S., Mucci, J., Liggitt, D., et al. (2013). Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORgammat and Ahr that leads to IL-17 production by activated B cells. Nat. Immunol.14,514-522.
Biermer, M., Puro, R., and Schneider, R.J. (2003). Tumor necrosis factor alpha inhibition of hepatitis B virus replication involves disruption of capsid Integrity through activation of NF-kappaB. J. Virol.77, 4033-4042.
Blonska, M., and Lin, X. (2009). CARMA1-mediated NF-kappaB and JNK activation in lymphocytes. Immunol. Rev.228,199-211.
Boehme, K.W., and Compton, T. (2004). Innate sensing of viruses by toll-like receptors. J. Virol.78, 7867-7873.
Boettler, T., Spangenberg, H.C., Neumann-Haefelin, C., Panther, E., Urbani, S., Ferrari, C., Blum, H.E., von Weizsacker, F., and Thimme, R. (2005). T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection. J. Virol.79, 7860-7867.
Brackett, C., Maier, P., Ramsey, K., and Gollnick, S. (2009). Photodynamic Therapy Elicited Adaptive Immunity is Critically Dependent on IL-17 Bioactivity. J. Immunol.182,41.56-.
Brucklacher-Waldert, V, Stuerner, K., Kolster, M., Wolthausen, J., and Tolosa, E. (2009). Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis. Brain 132,3329-3341.
Campbell, P.M., Pimm, J., Ramassar, V, and Halloran, P.F. (1996). Identification of a calcium-inducible, cyclosporine sensitive element in the IFN-gamma promoter that is a potential NFAT binding site. Transplantation 61,933-939.
Cappello, P., Triebel, F., Iezzi, M., Caorsi, C., Quaglino, E., Lollini, P.L., Amici, A., Di Carlo, E., Musiani, P., Giovarelli, M., et al. (2003). LAG-3 enables DNA vaccination to persistently prevent mammary carcinogenesis in HER-2/neu transgenic BALB/c mice. Cancer Res.63,2518-2525.
Carey, I., D'Antiga, L., Bansal, S., Longhi, M.S., Ma, Y., Mesa, I.R., Mieli-Vergani, G., and Vergani, D. (2011). Immune and viral profile from tolerance to hepatitis B surface antigen clearance:a longitudinal study of vertically hepatitis B virus-infected children on combined therapy. J. Virol.85,2416-2428.
Chan, C.Y., Lee, S.D., and Lo, K.J. (2004). Legend of hepatitis B vaccination:the Taiwan experience. J. Gastroenterol. Hepatol.19,121-126.
Chan, H.L., Tang, J.L., Tam, W., and Sung, J.J. (2001). The efficacy of thymosin in the treatment of chronic hepatitis B virus infection:a meta-analysis. Aliment. Pharmacol. Ther.15,1899-1905.
Chang, J.J., Wightman, F., Bartholomeusz, A., Ayres, A., Kent, S.J., Sasadeusz, J., and Lewin, S.R. (2005). Reduced hepatitis B virus (HBV)-specific CD4+ T-cell responses in human immunodeficiency virus type 1-HBV-coinfected individuals receiving HBV-active antiretroviral therapy. J. Virol.79,3038-3051.
Chang, S.H., Park, H., and Dong, C. (2006). Actl adaptor protein is an immediate and essential signaling component of interleukin-17 receptor. J. Biol. Chem.281,35603-35607.
Chen, X., Zhang, W., Gao, W., Zou, Q., Feng, C., Liu, H., Zhou, C., Zhang, Y., and Wang, B. (2012). Hemokinin-1 as an adjuvant molecule enhancing humoral and memory responses to HBsAg DNA vaccination. Viral immunol.25,289-296.
Cheung, C.Y., Poon, L.L., Lau, A.S., Luk, W., Lau, Y.L., Shortridge, K.F., Gordon, S., Guan, Y., and Peiris, J.S. (2002). Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses:a mechanism for the unusual severity of human disease? Lancet 360,1831-1837.
Chisari, F.V., and Ferrari, C. (1995). Hepatitis B virus immunopathogenesis. Annu. Rev. Immunol.13,29-60.
Chow, Y.H., Chiang, B.L., Lee, Y.L., Chi, W.K., Lin, W.C., Chen, Y.T., and Tao, M.H. (1998). Development of Thl and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genes. J. Immunol.160,1320-1329.
Chow, Y.H., Huang, W.L., Chi, W.K., Chu, YD., and Tao, M.H. (1997). Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis B surface antigen and interleukin-2. J. Virol.71, 169-178.
Chowell, G., Bertozzi, S.M., Colchero, M.A., Lopez-Gatell, H., Alpuche-Aranda, C., Hernandez, M., and Miller, M.A. (2009). Severe respiratory disease concurrent with the circulation of H1N1 influenza. N. Engl. J. Med.361,674-679.
Crowe, S.R., Turner, S.J., Miller, S.C., Roberts, A.D., Rappolo, R.A., Doherty, P.C., Ely, K.H., and Woodland, D.L. (2003). Differential antigen presentation regulates the changing patterns of CD8+ T cell immunodominance in primary and secondary influenza virus infections. J. Exp. Med.198,399-410.
Cua, D.J., and Tato, C.M. (2010). Innate IL-17-producing cells:the sentinels of the immune system. Nat. Rev. Immunol.10,479-489.
Davis, H.L., McCluskie, M.J., Gerin, J.L., and Purcell, R.H. (1996). DNA vaccine for hepatitis B:evidence for immunogenicity in chimpanzees and comparison with other vaccines. Proc. Natl. Acad. Sci. U. S. A. 93,7213-7218.
de Jong, M.D., Tran, T.T., Truong, H.K., Vo, M.H., Smith, GJ., Nguyen, V.C., Bach, V.C., Phan, T.Q., Do, Q.H., Guan, Y., et al. (2005). Oseltamivir resistance during treatment of influenza A (H5N1) infection. N. Engl. J. Med.353,2667-2672.
Dong, C. (2008). Regulation and pro-inflammatory function of interleukin-17 family cytokines. Immunol. Rev.226,80-86.
Du, D.W., Jia, Z.S., Li, G.Y., and Zhou, Y.Y. (2003). HBV DNA vaccine with adjuvant cytokines induced specific immune responses against HBV infection. World J. Gastroenterol.9,108-111.
Du, X., Zheng, G., Jin, H., Kang, Y., Wang, J., Xiao, C., Zhang, S., Zhao, L., Chen, A., and Wang, B. (2007). The adjuvant effects of co-stimulatory molecules on cellular and memory responses to HBsAg DNA vaccination. J. Gene. Med.9,136-146.
Engelhardt, O.G., Sirma, H., Pandolfi, P.P., and Haller, O. (2004). Mxl GTPase accumulates in distinct nuclear domains and inhibits influenza A virus in cells that lack promyelocytic leukaemia protein nuclear bodies. J. Gen. Virol.85,2315-2326.
Ferrari, C., Bertoletti, A., Penna, A., Cavalli, A., Valli, A., Missale, G, Pilli, M., Fowler, P., Giuberti, T., Chisari, F.V., et al. (1991). Identification of immunodominant T cell epitopes of the hepatitis B virus nucleocapsid antigen. J. Clin. Invest.88,214-222.
Fisman, D.N., Savage, R., Gubbay, J., Achonu, C., Akwar, H., Farrell, D.J., Crowcroft, N.S., and Jackson, P. (2009). Older age and a reduced likelihood of 2009 H1N1 virus infection. N. Engl. J. Med.361, 2000-2001.
Furuichi, Y, Tokuyama, H., Ueha, S., Kurachi, M., Moriyasu, F., and Kakimi, K. (2005). Depletion of CD25+CD4+T cells (Tregs) enhances the HBV-specific CD8+ T cell response primed by DNA immunization. World J. Gastroenterol.11,3772-3777.
Gaffen, S.L. (2009). Structure and signalling in the IL-17 receptor family. Nat. Rev. Immunol.9,556-567.
Ganem, D., and Prince, A.M. (2004). Hepatitis B virus infection--natural history and clinical consequences. N. Engl. J. Med.350,1118-1129.
Ganguly, S., Liu, J., Pillai, V.B., Mittler, R.S., and Amara, R.R. (2010). Adjuvantive effects of anti-4-1BB agonist Ab and 4-1BBL DNA for a HIV-1 Gag DNA vaccine:different effects on cellular and humoral immunity. Vaccine 28,1300-1309.
Gao, R., Cao, B., Hu, Y., Feng, Z., Wang, D., Hu, W., Chen, J., Jie, Z., Qiu, H., Xu, K., et al. (2013). Human infection with a novel avian-origin influenza A (H7N9) virus. N. Engl. J. Med.368,1888-1897.
Garcia-Sastre, A., Egorov, A., Matassov, D., Brandt, S., Levy, D.E., Durbin, J.E., Palese, P., and Muster, T. (1998). Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252, 324-330.
Geng, S., Zhong, Y., Wang, S., Liu, H., Zou, Q., Xie, X., Li, C., Yu, Q., He, Z., and Wang, B. (2012). Amiloride enhances antigen specific CTL by faciliting HBV DNA vaccine entry into cells. PLoS One 7, e33015.
Ghoreschi, K., Laurence, A., Yang, X.P., Tato, C.M., McGeachy, M.J., Konkel, J.E., Ramos, H.L., Wei, L., Davidson, T.S., Bouladoux, N., et al. (2010). Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature 467,961-971.
Goubau, D., Deddouche, S., and Reis e Sousa, C. (2013). Cytosolic sensing of viruses. Immunity 38, 855-869.
Grabbe, S., and Schwarz, T. (1998). Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity. Immunol. Today 19,37-44.
Guidotti, L.G, Ishikawa, T., Hobbs, M.V., Matzke, B., Schreiber, R., and Chisari, F.V. (1996). Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 4,25-36.
Guidotti, L.G., Morris, A., Mendez, H., Koch, R., Silverman, R.H., Williams, B.R., and Chisari, F.V. (2002). Interferon-regulated pathways that control hepatitis B virus replication in transgenic mice. J. Virol.76, 2617-2621.
Guidotti, L.G, Rochford, R., Chung, J., Shapiro, M., Purcell, R., and Chisari, F.V. (1999). Viral clearance without destruction of infected cells during acute HBV infection. Science 284,825-829.
Harrington, L.E., Hatton, R.D., Mangan, P.R., Turner, H., Murphy, T.L., Murphy, K.M., and Weaver, C.T. (2005). Interleukin 17-producing CD4+effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat. Immunol.6,1123-1132.
Hay, A.J., and Hayden, F.G (2013). Oseltamivir resistance during treatment of H7N9 infection. Lancet 381, 2230-2232.
Heathcote, J., McHutchison, J., Lee, S., Tong, M., Benner, K., Minuk, G, Wright, T., Fikes, J., Livingston, B., Sette, A., et al. (1999). A pilot study of the CY-1899 T-cell vaccine in subjects chronically infected with hepatitis B virus. The CY1899 T Cell Vaccine Study Group. Hepatology 30,531-536.
Huang, C.H., Peng, S., He, L., Tsai, Y.C., Boyd, D.A., Hansen, T.H., Wu, T.C., and Hung, C.F. (2005). Cancer immunotherapy using a DNA vaccine encoding a single-chain trimer of MHC class I linked to an HPV-16 E6 immunodominant CTL epitope. Gene Ther.12,1180-1186.
Ishigame, H., Kakuta, S., Nagai, T., Kadoki, M., Nambu, A., Komiyama, Y., Fujikado, N., Tanahashi, Y, Akitsu, A., Kotaki, H., et al. (2009). Differential roles of interleukin-17A and-17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30,108-119.
Isogawa, M., Robek, M.D., Furuichi, Y, and Chisari, F.V. (2005). Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J. Virol.79,7269-7272.
Itoh, Y, Shinya, K., Kiso, M., Watanabe, T., Sakoda, Y., Hatta, M., Muramoto, Y, Tamura, D., Sakai-Tagawa, Y, Noda, T., et al. (2009). In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 460,1021-1025.
Iwasaki, A. (2012). A virological view of innate immune recognition. Annu. Rev. Microbiol.66,177-196.
Jafri, H.S., Chavez-Bueno, S., Mejias, A., Gomez, A.M., Rios, A.M., Nassi, S.S., Yusuf, M., Kapur, P., Hardy, R.D., Hatfield, J., et al. (2004). Respiratory Syncytial Virus Induces Pneumonia, Cytokine Response, Airway Obstruction, and Chronic Inflammatory Infiltrates Associated with Long-Term Airway Hyperresponsiveness in Mice. J. Infect. Dis.189,1856-1865.
Jelley-Gibbs, D.M., Brown, D.M., Dibble, J.P., Haynes, L., Eaton, S.M., and Swain, S.L. (2005). Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation. J. Exp. Med.202, 697-706.
Johansson, B.E., Bucher, D.J., and Kilbourne, E.D. (1989). Purified influenza virus hemagglutinin and neuraminidase are equivalent in stimulation of antibody response but induce contrasting types of immunity to infection. J. Virol.63,1239-1246.
Kakimi, K., Guidotti, L.G, Koezuka, Y, and Chisari, F.V. (2000). Natural killer T cell activation inhibits hepatitis B virus replication in vivo. J. Exp. Med.192,921-930.
Kakimi, K., Isogawa, M., Chung, J., Sette, A., and Chisari, F.V. (2002). Immunogenicity and tolerogenicity of hepatitis B virus structural and nonstructural proteins:implications for immunotherapy of persistent viral infections. J. Virol.76,8609-8620.
Kim, S.J., Suh, D., Park, S.E., Park, J.S., Byun, H.M., Lee, C., Lee, S.Y., Kim, I., and Oh, Y.K. (2003). Enhanced immunogenicity of DNA fusion vaccine encoding secreted hepatitis B surface antigen and chemokine RANTES. Virology 314,84-91.
Kimura, K., Kakimi, K., Wieland, S., Guidotti, L.G., and Chisari, F.V. (2002a). Activated intrahepatic antigen-presenting cells inhibit hepatitis B virus replication in the liver of transgenic mice. J. Immunol. 169,5188-5195.
Kimura, K., Kakimi, K., Wieland, S., Guidotti, L.G, and Chisari, F.V. (2002b). Interleukin-18 inhibits hepatitis B virus replication in the livers of transgenic mice. J. Virol.76,10702-10707.
Kimura, K., Kakimi, K., Wieland, S., Guidotti, L.G, and Chisari, F.V. (2002c). Interleukin-18 inhibits hepatitis B virus replication in the livers of transgenic mice. J. Virol.76,10702-10707.
Kinter, A.L., Hennessey, M., Bell, A., Kern, S., Lin, Y., Daucher, M., Planta, M., McGlaughlin, M., Jackson, R., Ziegler, S.F., et al. (2004). CD25(+)CD4(+) regulatory T cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4(+) and CD8(+) HIV-specific T cell immune responses in vitro and are associated with favorable clinical markers of disease status. J. Exp. Med.200, 331-343.
Kirkham, B.W., Kavanaugh, A., and Reich, K. (2014). Interleukin-17A:a unique pathway in immune-mediated diseases:psoriasis, psoriatic arthritis and rheumatoid arthritis. Immunology 141, 133-142.
Kutzler, M.A., and Weiner, D.B. (2008). DNA vaccines:ready for prime time? Nat. Rev. Genet.9,776-788.
Lambrecht, B.N., Kool, M., Willart, M.A., and Hammad, H. (2009). Mechanism of action of clinically approved adjuvants. Curr. Opin. Immunol.21,23-29.
Langrish, C.L., Chen, Y., Blumenschein, W.M., Mattson, J., Basham, B., Sedgwick, J.D., McClanahan, T., Kastelein, R.A., and Cua, D.J. (2005). IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med.201,233-240.
Lee, Y.K., Turner, H., Maynard, C.L., Oliver, J.R., Chen, D., Elson, C.O., and Weaver, C.T. (2009). Late developmental plasticity in the T helper 17 lineage. Immunity 30,92-107.
Legge, K.L., and Braciale, T.J. (2003). Accelerated migration of respiratory dendritic cells to the regional lymph nodes is limited to the early phase of pulmonary infection. Immunity 18,265-277.
Li, J., Qiu, S.J., She, W.M., Wang, F.P., Gao, H., Li, L., Tu, C.T., Wang, J.Y., Shen, X.Z., and Jiang, W. (2012). Significance of the balance between regulatory T (Treg) and T helper 17 (Th17) cells during hepatitis B virus related liver fibrosis. PLoS One 7, e39307.
Li, J., Wu, W., Peng, G, Chen, F., Bai, M., Zheng, M., and Chen, Z. (2010). HBcAg induces interleukin-10 production, inhibiting HBcAg-specific Th17 responses in chronic hepatitis B patients. Immunol. Cell. Biol.88,834-841.
Li, M.J., Lei, J.H., Wang, T., Lu, S.J., Guan, F., Liu, W.Q., and Li, Y.L. (2011). Cimetidine enhances the protective effect of GST DNA vaccine against Schistosoma japonicum. Exp. Parasitol.128,427-432.
Liang, M, Ma, S., Hu, X., Zhou, B., Zhang, J., Chen, J., Wang, Z., Sun, J., Zhu, X., Abbott, W., et al. (2011). Cellular immune responses in patients with hepatitis B surface antigen seroclearance induced by antiviral therapy. Virol. J.8,69.
Lindemann, M.J., Hu, Z., Benczik, M., Liu, K.D., and Gaffen, S.L. (2008). Differential regulation of the IL-17 receptor by gammac cytokines:inhibitory signaling by the phosphatidylinositol 3-kinase pathway. J. Biol. Chem.283,14100-14108.
Lindstrom, S.E., Cox, N.J., and Klimov, A. (2004). Genetic analysis of human H2N2 and early H3N2 influenza viruses,1957-1972:evidence for genetic divergence and multiple reassortment events. Virology 328,101-119.
Liu, L., Huang, D., Matsui, M., He, T.T., Hu, T., Demartino, J., Lu, B., Gerard, C, and Ransohoff, R.M. (2006). Severe disease, unaltered leukocyte migration, and reduced IFN-gamma production in CXCR3-/-mice with experimental autoimmune encephalomyelitis. J. Immunol.176,4399-4409.
Lock, C., Hermans, G., Pedotti, R., Brendolan, A., Schadt, E., Garren, H., Langer-Gould, A., Strober, S., Cannella, B., Allard, J., et al. (2002). Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med.8,500-508.
Lok, A.S. (2002). Chronic hepatitis B. N. Engl. J. Med.346,1682-1683.
Ma, R., Du, J.L., Huang, J., and Wu, C.Y. (2007). Additive effects of CpG ODN and R-848 as adjuvants on augmenting immune responses to HBsAg vaccination. Biochem. Biophys. Res. Commun.361,537-542.
MacGregor, R.R., Boyer, J.D., Ugen, K.E., Lacy, K.E., Gluckman, S.J., Bagarazzi, M.L., Chattergoon, M.A., Baine, Y., Higgins, T.J., Ciccarelli, R.B., et al. (1998). First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection:safety and host response. The J. Infect. Dis.178,92-100.
Maini, M.K., Boni, C., Lee, C.K., Larrubia, J.R., Reignat, S., Ogg, G.S., King, A.S., Herberg, J., Gilson, R., Alisa, A., et al. (2000). The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. J. Exp. Med.191,1269-1280.
Maini, M.K., Boni, C., Ogg, G.S., King, A.S., Reignat, S., Lee, C.K., Larrubia, J.R., Webster, G.J., McMichael, A.J., Ferrari, C., et al. (1999). Direct ex vivo analysis of hepatitis B virus-specific CD8(+) T cells associated with the control of infection. Gastroenterology 117,1386-1396.
Maitra, A., Shen, F., Hanel, W., Mossman, K., Tocker, J., Swart, D., and Gaffen, S.L. (2007). Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression. Proc. Natl. Acad. Sci. U. S. A.104,7506-7511.
Mancini, M., Hadchouel, M., Davis, H.L., Whalen, R.G., Tiollais, P., and Michel, M.L. (1996). DNA-mediated immunization in a transgenic mouse model of the hepatitis B surface antigen chronic carrier state. Proc. Natl. Acad. Sci. U. S. A.93,12496-12501.
Matusevicius, D., Kivisakk, P., He, B., Kostulas, N., Ozenci, V., Fredrikson, S., and Link, H. (1999). Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult. Scler.5,101-104.
McGeachy, M.J., Bak-Jensen, K.S., Chen, Y., Tato, C.M., Blumenschein, W., McClanahan, T., and Cua, D.J. (2007). TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat. Immunol.8,1390-1397.
Mejias, A., Chavez-Bueno, S., Rios, A.M., Saavedra-Lozano, J., Fonseca Aten, M., Hatfield, J., Kapur, P., Gomez, A.M., Jafri, H.S., and Ramilo, O. (2004). Anti-Respiratory Syncytial Virus (RSV) Neutralizing Antibody Decreases Lung Inflammation, Airway Obstruction, and Airway Hyperresponsiveness in a Murine RSV Model. Antimicrob. Agents Chemother.48,1811-1822.
Mizukoshi, E., Sidney, J., Livingston, B., Ghany, M., Hoofhagle, J.H., Sette, A., and Rehermann, B. (2004). Cellular immune responses to the hepatitis B virus polymerase. J. Immunol.173,5863-5871.
Morefield, G.L., Sokolovska, A., Jiang, D., HogenEsch, H., Robinson, J.P., and Hem, S.L. (2005). Role of aluminum-containing adjuvants in antigen internalization by dendritic cells in vitro. Vaccine 23, 1588-1595.
Morens, D.M., Folkers, G.K., and Fauci, A.S. (2004). The challenge of emerging and re-emerging infectious diseases. Nature 430,242-249.
Moscona, A. (2005). Oseltamivir resistance--disabling our influenza defenses. N. Engl. J. Med.353, 2633-2636.
Munks, M.W., Mourich, D.V., Mittler, R.S., Weinberg, A.D., and Hill, A.B. (2004).4-1BB and OX40 stimulation enhance CD8 and CD4 T-cell responses to a DNA prime, poxvirus boost vaccine. Immunology 112,559-566.
Murray, J.M., Wieland, S.F., Purcell, R.H., and Chisari, F.V. (2005). Dynamics of hepatitis B virus clearance in chimpanzees. Proc. Natl. Acad. Sci. U. S. A.102,17780-17785.
O'Mahony, L., Akdis, M., and Akdis, C.A. (2011). Regulation of the immune response and inflammation by histamine and histamine receptors. J. Allergy Clin. Immunol.128,1153-1162.
O'Shea, J.J., and Paul, W.E. (2010). Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 327,1098-1102.
Ouyang, W., Kolls, J.K., and Zheng, Y. (2008). The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28,454-467.
Pan, C.Q., and Zhang, J.X. (2005). Natural History and Clinical Consequences of Hepatitis B Virus Infection. Int. J. Med. Sci.2,36-40.
Pancholi, P., Lee, D.H., Liu, Q., Tackney, C., Taylor, P., Perkus, M., Andrus, L., Brotman, B., and Prince, A.M. (2001). DNA prime/canarypox boost-based immunotherapy of chronic hepatitis B virus infection in a chimpanzee. Hepatology 33,448-454.
Papatheodoridis, G.V., Dimou, E., and Papadimitropoulos, V. (2002). Nucleoside analogues for chronic hepatitis B:antiviral efficacy and viral resistance. Am. J. Gastroenterol.97,1618-1628.
Park, H., Li, Z., Yang, X.O., Chang, S.H., Nurieva, R., Wang, Y.H., Wang, Y, Hood, L., Zhu, Z., Tian, Q., et al. (2005). A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol.6,1133-1141.
Partridge, J., and Kieny, M.P. (2013). Global production capacity of seasonal influenza vaccine in 2011. Vaccine 31,728-731.
Pearce, E.L., Mullen, A.C., Martins, GA., Krawczyk, C.M., Hutchins, A.S., Zediak, V.P., Banica, M., DiCioccio, C.B., Gross, D.A., Mao, C.A., et al. (2003). Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science 302,1041-1043.
Penix, L.A., Sweetser, M.T., Weaver, W.M., Hoeffler, J.P., Kerppola, T.K., and Wilson, C.B. (1996). The proximal regulatory element of the interferon-gamma promoter mediates selective expression in T cells. J. Biol. Chem.271,31964-31972.
Penna, A., Artini, M., Cavalli, A., Levrero, M., Bertoletti, A., Pilli, M., Chisari, F.V., Rehermann, B., Del Prete, G., Fiaccadori, F., et al. (1996). Long-lasting memory T cell responses following self-limited acute hepatitis B. J. Clin. Invest.98,1185-1194.
Penna, A., Del Prete, G., Cavalli, A., Bertoletti, A., D'Elios, M.M., Sorrentino, R., D'Amato, M., Boni, C., Pilli, M., Fiaccadori, F., et al. (1997). Predominant T-helper 1 cytokine profile of hepatitis B virus nucleocapsid-specific T cells in acute self-limited hepatitis B. Hepatology 25,1022-1027.
Pignatelli, M., Waters, J., Lever, A., Iwarson, S., Gerety, R., and Thomas, H.C. (1987). Cytotoxic T-Cell Responses to the Nucleocapsid Proteins of Hbv in Chronic Hepatitis-Evidence That Antibody Modulation May Cause Protracted Infection. J. Hepatol.4,15-21.
Pol, S., Driss, F., Michel, M.L., Nalpas, B., Berthelot, P., and Brechot, C. (1994). Specific vaccine therapy in chronic hepatitis B infection. Lancet 344,342.
Reed, S.G., Bertholet, S., Coler, R.N., and Friede, M. (2009). New horizons in adjuvants for vaccine development. Trends Immunol.30,23-32.
Rehermann, B., Fowler, P., Sidney, J., Person, J., Redeker, A., Brown, M., Moss, B., Sette, A., and Chisari, F.V. (1995). The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis. J. Exp. Med.181,1047-1058.
Rehermann, B., Lau, D., Hoofnagle, J.H., and Chisari, F.V. (1996). Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection. J. Clin. Invest.97,1655-1665.
Rehermann, B., and Nascimbeni, M. (2005). Immunology of hepatitis B virus and hepatitis C virus infection. Nat. Rev. Immunol.5,215-229.
Reignat, S., Webster, G.J., Brown, D., Ogg, GS., King, A., Seneviratne, S.L., Dusheiko, G, Williams, R., Maini, M.K., and Bertoletti, A. (2002). Escaping high viral load exhaustion:CD8 cells with altered tetramer binding in chronic hepatitis B virus infection. J. Exp. Med.195,1089-1101.
Roth, E., and Pircher, H. (2004). IFN-gamma promotes Fas ligand- and perforin-mediated liver cell destruction by cytotoxic CD8 T cells. J. Immunol.172,1588-1594.
Ruddy, M.J., Wong, G.C., Liu, X.K., Yamamoto, H., Kasayama, S., Kirkwood, K.L., and Gaffen, S.L. (2004). Functional cooperation between interleukin-17 and tumor necrosis factor-alpha is mediated by CCAAT/enhancer-binding protein family members. J. Biol. Chem.279,2559-2567.
Sasaki, M., Foccacia, R., and de Messias-Reason, I.J. (2003). Efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant for hepatitis B virus in patients with HIV infection. Vaccine 21,4545-4549.
Schwandner, R., Yamaguchi, K., and Cao, Z. (2000). Requirement of tumor necrosis factor receptor-associated factor (TRAF)6 in interleukin 17 signal transduction. J. Exp. Med.191,1233-1240.
Sealy, R., Surman, S., Hurwitz, J.L., and Coleclough, C. (2003). Antibody response to influenza infection of mice:different patterns for glycoprotein and nucleocapsid antigens. Immunology 108,431-439.
Shen, F., Ruddy, M.J., Plamondon, P., and Gaffen, S.L. (2005). Cytokines link osteoblasts and inflammation: microarray analysis of interleukin-17- and TNF-alpha-induced genes in bone cells. J. Leukoc. Biol.77, 388-399.
Shi, T.D., Wu, Y.Z., Jia, Z.C., Zou, L.Y., and Zhou, W. (2004). Therapeutic polypeptides based on HBV core 18-27 epitope can induce CD8+ CTL-mediated cytotoxicity in HLA-A2+ human PBMCs. World J. Gastroenterol.10,1902-1906.
Sica, A., Dorman, L., Viggiano, V., Cippitelli, M., Ghosh, P., Rice, N., and Young, H.A. (1997). Interaction of NF-kappaB and NFAT with the interferon-gamma promoter. J. Biol. Chem.272,30412-30420.
Spanaus, K.S., Schlapbach, R., and Fontana, A. (1998). TNF-alpha and IFN-gamma render microglia sensitive to Fas ligand-induced apoptosis by induction of Fas expression and down-regulation of Bcl-2 and Bcl-xL. European J. Immunol.28,4398-4408.
Sprengers, D., van der Molen, R.G., Kusters, J.G, Hansen, B., Niesters, H.G, Schalm, S.W., and Janssen, H.L. (2006). Different composition of intrahepatic lymphocytes in the immune-tolerance and immune-clearance phase of chronic hepatitis B. J. Med. Virol.78,561-568.
Stoop, J.N., van der Molen, R.G., Baan, C.C., van der Laan, L.J., Kuipers, E.J., Kusters, J.G., and Janssen, H.L. (2005). Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology 41,771-778.
Subbarao, K., and Joseph, T. (2007). Scientific barriers to developing vaccines against avian influenza viruses. Nat. Rev. Immunol.7,267-278.
Sweetser, M.T., Hoey, T., Sun, Y.L., Weaver, W.M., Price, GA., and Wilson, C.B. (1998). The roles of nuclear factor of activated T cells and ying-yang 1 in activation-induced expression of the interferon-gamma promoter in T cells. J. Biol. Chem.273,34775-34783.
Szabo, S.J., Kim, S.T., Costa, G.L., Zhang, X., Fathman, C.G., and Glimcher, L.H. (2000). A novel transcription factor, T-bet, directs Thl lineage commitment. Cell 100,655-669.
Szabo, S.J., Sullivan, B.M., Stemmann, C., Satoskar, A.R., Sleckman, B.P., and Glimcher, L.H. (2002). Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 295,338-342.
Tacket, C.O., Roy, M.J., Widera, G., Swain, W.F., Broome, S., and Edelman, R. (1999). Phase 1 safety and immune response studies of a DNA vaccine encoding hepatitis B surface antigen delivered by a gene delivery device. Vaccine 17,2826-2829.
Takatori, H., Kanno, Y., Watford, W.T., Tato, C.M., Weiss, G., Ivanov, Ⅱ, Littman, D.R., and O'Shea, J.J. (2009). Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J. Exp. Med.206, 35-41.
Tang, T.J., Kwekkeboom, J., Laman, J.D., Niesters, H.G., Zondervan, P.E., de Man, R.A., Schalm, S.W., and Janssen, H.L. (2003). The role of intrahepatic immune effector cells in inflammatory liver injury and viral control during chronic hepatitis B infection. J. Viral Hepat.10,159-167.
Tarr, P.E., Lin, R., Mueller, E.A., Kovarik, J.M., Guillaume, M., and Jones, T.C. (1996). Evaluation of tolerability and antibody response after recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and a single dose of recombinant hepatitis B vaccine. Vaccine 14,1199-1204.
Thimme, R., Wieland, S., Steiger, C., Ghrayeb, J., Reimann, K.A., Purcell, R.H., and Chisari, F.V. (2003). CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J. Virol.77,68-76.
Townsend, M.J., Weinmann, A.S., Matsuda, J.L., Salomon, R., Farnham, P.J., Biron, C.A., Gapin, L., and Glimcher, L.H. (2004). T-bet regulates the terminal maturation and homeostasis of NK and Valphal4i NKT cells. Immunity 20,477-494.
Tripp, R.A., Topham, D.J., Watson, S.R., and Doherty, P.C. (1997). Bone marrow can function as a lymphoid organ during a primary immune response under conditions of disrupted lymphocyte trafficking. J. Immunol.158,3716-3720.
Tumpey, T.M., Garcia-Sastre, A., Taubenberger, J.K., Palese, P., Swayne, D.E., Pantin-Jackwood, M.J., Schultz-Cherry, S., Solorzano, A., Van Rooijen, N., Katz, J.M., et al. (2005). Pathogenicity of influenza viruses with genes from the 1918 pandemic virus:functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice. J. Virol.79,14933-14944.
Turan, K., Mibayashi, M., Sugiyama, K., Saito, S., Numajiri, A., and Nagata, K. (2004). Nuclear MxA proteins form a complex with influenza virus NP and inhibit the transcription of the engineered influenza virus genome. Nucleic Acids Res.32,643-652.
van Zonneveld, M., Honkoop, P., Hansen, B.E., Niesters, H.G., Darwish Murad, S., de Man, R.A., Schalm, S.W., and Janssen, H.L. (2004). Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology 39,804-810.
Vignali, D.A., Collison, L.W., and Workman, C.J. (2008). How regulatory T cells work. Nat. Rev. Immunol. 8,523-532.
Wang, J., Su, B., Ding, Z., Du, X., and Wang, B. (2008). Cimetidine enhances immune response of HBV DNA vaccination via impairment of the regulatory function of regulatory T cells. Biochem. Biophys. Res. Commun.372,491-496.
Watanabe, K., Mwinzi, P.N., Black, C.L., Muok, E.M., Karanja, D.M., Secor, W.E., and Colley, D.G. (2007). T regulatory cell levels decrease in people infected with Schistosoma mansoni on effective treatment. Am. J. Trop. Med. Hyg.77,676-682.
Webster, GJ., Reignat, S., Maini, M.K., Whalley, S.A., Ogg, GS., King, A., Brown, D., Amlot, P.L., Williams, R., Vergani, D., et al. (2000). Incubation phase of acute hepatitis B in man:dynamic of cellular immune mechanisms. Hepatology 32,1117-1124.
Webster, R.G., Bean, W.J., Gorman, O.T., Chambers, T.M., and Kawaoka, Y. (1992). Evolution and ecology of influenza A viruses. Microbiol. Rev.56,152-179.
Wen, Y.M., Wu, X.H., Hu, D.C., Zhang, Q.P., and Guo, S.Q. (1995). Hepatitis B vaccine and anti-HBs complex as approach for vaccine therapy. Lancet 345,1575-1576.
Wherry, E.J., Blattman, J.N., Murali-Krishna, K., van der Most, R., and Ahmed, R. (2003). Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J. Virol.77,4911-4927.
Wieland, S.F., Guidotti, L.G, and Chisari, F.V. (2000). Intrahepatic induction of alpha/beta interferon eliminates viral RNA-containing capsids in hepatitis B virus transgenic mice. J. Virol.74,4165-4173.
Wong, D.K., Cheung, A.M., O'Rourke, K., Naylor, C.D., Detsky, A.S., and Heathcote, J. (1993). Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann. Intern. Med.119,312-323.
Workman, C.J., Szymczak-Workman, A.L., Collison, L.W., Pillai, M.R., and Vignali, D.A. (2009). The development and function of regulatory T cells. Cell. Mol. Life Sci.66,2603-2622.
Wu, B., Zou, Q., Hu, Y., and Wang, B. (2013). Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8(+) T cell responses against a HBV DNA vaccine in mice. Hum. Vaccin. Immunother.9.
Xu, D.Z., Huang, K.L., Zhao, K., Xu, L.F., Shi, N., Yuan, Z.H., and Wen, Y.M. (2005). Vaccination with recombinant HBsAg-HBIG complex in healthy adults. Vaccine 23,2658-2664.
Xu, D.Z., Zhao, K., Guo, L.M., Li, L.J., Xie, Q., Ren, H., Zhang, J.M., Xu, M., Wang, H.F., Huang, W.X., et al. (2008). A randomized controlled phase Ⅱb trial of antigen-antibody immunogenic complex therapeutic vaccine in chronic hepatitis B patients. PLoS One 3, e2565.
Yamazaki, S., Muta, T., Matsuo, S., and Takeshige, K. (2005). Stimulus-specific induction of a novel nuclear factor-kappaB regulator, IkappaB-zeta, via Toll/Interleukin-1 receptor is mediated by mRNA stabilization. J. Biol. Chem.280,1678-1687.
Yan, H., Zhong, G., Xu, G, He, W., Jing, Z., Gao, Z., Huang, Y, Qi, Y, Peng, B., Wang, H., et al. (2012). Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife 1, e00049.
Yao, Z., Fanslow, W.C., Seldin, M.F., Rousseau, A.M., Painter, S.L., Comeau, M.R., Cohen, J.I., and Spriggs, M.K. (1995). Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 3,811-821.
Ye, J., Su, X., Hsueh, E.C., Zhang, Y, Koenig, J.M., Hoft, D.F., and Peng, G. (2011). Human tumor-infiltrating Th17 cells have the capacity to differentiate into IFN-gamma+ and FOXP3+ T cells with potent suppressive function. European J. Immunol.41,936-951.
Yu, H., Cowling, B.J., Feng, L., Lau, E.H., Liao, Q., Tsang, T.K., Peng, Z., Wu, P., Liu, F., Fang, V.J, et al. (2013). Human infection with avian influenza A H7N9 virus:an assessment of clinical severity. Lancet 382,138-145.
Yu, J.J., and Gaffen, S.L. (2008). Interleukin-17:a novel inflammatory cytokine that bridges innate and adaptive immunity. Front, biosci.13,170-177.
Zhang, J.Y., Song, C.H., Shi, F., Zhang, Z., Fu, J.L., and Wang, F.S. (2010). Decreased ratio of Treg cells to Th17 cells correlates with HBV DNA suppression in chronic hepatitis B patients undergoing entecavir treatment. PLoS One 5, e13869.
Zhang, Q., Shi, J., Deng, G, Guo, J., Zeng, X., He, X., Kong, H., Gu, C., Li, X., Liu, J., et al. (2013). H7N9 influenza viruses are transmissible in ferrets by respiratory droplet. Science 341,410-414.
Zhang, W., Du, X., Zhao, G, Jin, H., Kang, Y., Xiao, C., Liu, M., and Wang, B. (2009). Levamisole is a potential facilitator for the activation of Thl responses of the subunit HBV vaccination. Vaccine 27, 4938-4946.
Zhang, X., Yu, C., Zhao, J., Fu, L., Yi, S., Liu, S., Yu, T., and Chen, W. (2007). Vaccination with a DNA vaccine based on human PSCA and HSP70 adjuvant enhances the antigen-specific CD8+ T-cell response and inhibits the PSCA+ tumors growth in mice. J. Gene. Med.9,715-726.
Zhu, Z., Yang, Y., Feng, Y, Shi, B., Chen, L., Zheng, Y, Tian, D., Song, Z., Xu, C., Qin, B., et al. (2013). Infection of inbred BALB/c and C57BL/6 and outbred Institute of Cancer Research mice with the emerging H7N9 avian influenza virus. Emerg. Microbes Infect.2, e50.
Zou, Q., Hu, Y, Xue, J., Fan, X., Jin, Y, Shi, X., Meng, D., Wang, X., Feng, C., Xie, X., et al. (2012). Use of praziquantel as an adjuvant enhances protection and Tc-17 responses to killed H5N1 virus vaccine in mice. PLoS One 7, e34865.
Zou, Q., Yao, X., Feng, J., Yin, Z., Flavell, R., Hu, Y, Zheng, G, Jin, J., Kang, Y, Wu, B., et al. (2011). Praziquantel facilitates IFN-gamma-producing CD8+ T cells (Tcl) and IL-17-producing CD8+ T cells (Tc17) responses to DNA vaccination in mice. PLoS One 6, e25525.
Zou, Q., Zhong, Y, Su, H., Kang, Y, Jin, J., Liu, Q., Geng, S., Zhao, G, and Wang, B. (2010). Enhancement of humoral and cellular responses to HBsAg DNA vaccination by immunization with praziquantel through inhibition TGF-beta/Smad2,3 signaling. Vaccine 28,2032-2038.
王晓军,张荣珍,胡苑笙,梁晓峰(2004).我国病毒性肝炎流行现状研究.疾病监测19,290-292.
杨富强,陈光明,饶桂荣,徐宇虹,赵勇刚,何晓嫱,孙希海,侯金林(2008). IL-2/IFN-γ融合蛋白基因质粒联合HBV DNA疫苗治疗HBV转基因小鼠效果评价.热带医学杂志,408-411.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |