NOD鼠体内CD_4~+NKG2D~+T细胞与CD_8~+T细胞间关系
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摘要
目的探讨NOD鼠体内CD_4~+NKG2D~+T细胞与CD_8~+T细胞间关系。方法动态监测NOD鼠外周血中CD_4~+NKG2D~+T及CD8+NKG2D~+T细胞在不同周龄频率。利用IGRP206-214特异性CTL清除的NOD鼠,对其外周血中CD_4~+NKG2D+/CD_4~+T及CD8+NKG2D+/CD_8~+T细胞频率进行分析。将磁珠分选所得CD_4~+NKG2D~+T细胞分别与经CFSE标记的纯CD_4~+NKG2D-T细胞、CD_8~+T细胞共培养4 d,检测体系中CD_4~+NKG2D-T细胞、CD_8~+T细胞CFSE的荧光强度变化。结果 NOD鼠外周血CD_4~+NKG2D+/CD_4~+T及CD8+NKG2D+/CD_8~+T细胞频率均随其1型糖尿病疾病进程发展逐渐升高,且二者之间呈正相关。IGRP206-214特异性CTL清除的NOD鼠,外周血中CD_4~+NKG2D+/CD_4~+T细胞频率随CD8+NKG2D+/CD_8~+T细胞频率降低显著下降。与单独培养的CD_4~+NKG2D-T细胞相比,加入CD_4~+NKG2D~+T细胞的培养体系中,CD_4~+NKG2D-T细胞增殖加快。但CD_4~+NKG2D~+T细胞对CD_8~+T增殖作用不明显。结论 NOD鼠体内存在着一群与1型糖尿病疾病进程正相关的CD_4~+NKG2D~+T细胞,且该群细胞极有可能是通过直接作用于CD_4~+NKG2D-T细胞而间接对CD_8~+T细胞产生作用。
Objective To explore the relationship between CD_4~+NKG2D~+T and CD_8~+T cells in NOD rats. Methods The frequency of CD_4~+NKG2D~+T and CD8+NKG2D~+T cells in peripheral blood of NOD rats in different weeks were dynamically monitored. By using IGRP206- 214- SAP NOD rats,the frequencies of CD_4~+NKG2D+/ CD_4~+T and CD8+NKG2D+/ CD_8~+T cells in peripheral blood were analyzed. CD_4~+NKG2D~+T cells was purified and CFSE CD_4~+NKG2D-T cells or CD_8~+T were co-cultured 4 days were marked. The CFSE fluorescence intensity change of CD_4~+NKG2D-T cells or CD_8~+T cells were detected. Results The frequency of CD_4~+NKG2D+/ CD_4~+T and CD8+NKG2D+/ CD_8~+T cells in peripheral blood of female NOD rats during the development of type 1 diabetes disease process gradually increased,and they were positively correlated to the linear.In the NOD rats with IGRP206- 214-SAP,the frequency of CD_4~+NKG2D+/ CD_4~+T cells in peripheral blood was reduced by CD8+NKG2D+/ CD_8~+T cells reduction. Compared with alone CD_4~+NKG2DT cells,the proliferation of CD_4~+NKG2D-T cells was speeded up in cell culture system incubated with CD_4~+NKG2D~+T. CD_4~+NKG2D~+T cells is no direct effect on the CD_8~+T cell. Conclusion An increased CD_4~+NKG2D~+T cells subsets in NOD mice might have an effect on CD_8~+T cells through activation of CD_4~+NKG2D-T cells.
Objective To explore the relationship between CD_4~+NKG2D~+T and CD_8~+T cells in NOD rats. Methods The frequency of CD_4~+NKG2D~+T and CD8+NKG2D~+T cells in peripheral blood of NOD rats in different weeks were dynamically monitored. By using IGRP206- 214- SAP NOD rats,the frequencies of CD_4~+NKG2D+/ CD_4~+T and CD8+NKG2D+/ CD_8~+T cells in peripheral blood were analyzed. CD_4~+NKG2D~+T cells was purified and CFSE CD_4~+NKG2D-T cells or CD_8~+T were co-cultured 4 days were marked. The CFSE fluorescence intensity change of CD_4~+NKG2D-T cells or CD_8~+T cells were detected. Results The frequency of CD_4~+NKG2D+/ CD_4~+T and CD8+NKG2D+/ CD_8~+T cells in peripheral blood of female NOD rats during the development of type 1 diabetes disease process gradually increased,and they were positively correlated to the linear.In the NOD rats with IGRP206- 214-SAP,the frequency of CD_4~+NKG2D+/ CD_4~+T cells in peripheral blood was reduced by CD8+NKG2D+/ CD_8~+T cells reduction. Compared with alone CD_4~+NKG2DT cells,the proliferation of CD_4~+NKG2D-T cells was speeded up in cell culture system incubated with CD_4~+NKG2D~+T. CD_4~+NKG2D~+T cells is no direct effect on the CD_8~+T cell. Conclusion An increased CD_4~+NKG2D~+T cells subsets in NOD mice might have an effect on CD_8~+T cells through activation of CD_4~+NKG2D-T cells.
引文
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[14]王贵渠,赵琎,徐海伟,等.C57BL/6.NOD-Aec1Aec2干燥综合征模型小鼠干眼表型及性别差异研究[J].第三军医大学学报,2015,37(9):876-880.
[15]邵玲巧,王倩倩,郭圆圆,等.NOD/SCID小鼠中A431侧群与非侧群细胞成瘤组织中EMT相关分子的表达[J].南方医科大学学报,2013,33(5):733-737.
[2]Van Belle T L,Coppieters K T,Von Herrath M G.Type 1diabetes:etiology,immunology,and therapeutic strategies[J].Physiological reviews,2011,91(1):79-118.
[3]Ogasawara K,Hamerman J A,Hsin H,et al.Impairment of NK cell function by NKG2D modulation in NOD mice[J].Immunity,2003,18(1):41-51.
[4]Ogasawara K,Hamerman J A,Ehrlich L R,et al.NKG2D blockade prevents autoimmune diabetes in NOD mice[J].Immunity,2004,20(6):757-767.
[5]Anderson M S,Bluestone J A.The NOD mouse:a model of immune dysregulation[J].Annu Rev Immunol,2005,23:447-485.
[6]Sharma N,Markiewicz M A.Constitutive expression of the NKG2D ligand RAE1 within pancreatic islets ameliorates autoimmune diabetes development in non-obese diabetic mice[J].The Journal of Immunology,2016,196(1 Suppl):49-59.
[7]Van Belle T L,Ling E,Haase C,et al.NKG2D blockade facilitates diabetes prevention by antigen-specific Tregs in a virus-induced model of diabetes[J].Journal of autoimmunity,2013,40:66-73.
[8]Rodacki M,Svoren B,Butty V,et al.Altered natural killer cells in type 1 diabetic patients[J].Diabetes,2007,56(1):177-185.
[9]Garcia-Chagollan M,Jave-Suarez L F,Haramati J,et al.An approach to the immunophenotypic features of circulating CD4+NKG2D+T cells in invasive cervical carcinoma[J].Journal of biomedical science,2015,22(1):1-12.
[10]Wiemann K,Mittrücker H W,Feger U,et al.Systemic NKG2D down-regulation impairs NK and CD8T cell responses in vivo[J].The Journal of Immunology,2005,175(2):720-729.
[11]Kerstein,Müller,Kabelitz,et al.Effector memory T-cells in the pathogenesis of ANCA-associated vasculitides[J].Springer-Verlag Berlin Heidelberg,2016,75(2):183-6.
[12]庞春艳,吕凤凤,杨麟,等.α-胞衬蛋白siRNA对干燥综合征模型NOD小鼠IFN-γ和IL-4表达水平及基因沉默效果的影响[J].吉林大学学报:医学版,2013,39(3):548-553.
[13]胡旭君,宋欣伟.雷公藤多苷联合甲氨蝶呤对干燥综合征NOD小鼠治疗作用及TNF-α、IL-1β、AQP-5的表达[J].中华中医药杂志,2014(7):2362-2366.
[14]王贵渠,赵琎,徐海伟,等.C57BL/6.NOD-Aec1Aec2干燥综合征模型小鼠干眼表型及性别差异研究[J].第三军医大学学报,2015,37(9):876-880.
[15]邵玲巧,王倩倩,郭圆圆,等.NOD/SCID小鼠中A431侧群与非侧群细胞成瘤组织中EMT相关分子的表达[J].南方医科大学学报,2013,33(5):733-737.