NOD小鼠人源化后CD4^+T和CD8^+T细胞及其分泌IFN-γ与IL-17的频率变化及意义  

The difference and significance of the frequencies of CD3^+CD4^+T and CD3^+CD8^+T cells and their IFN-γ or IL-17 secretion between humanized NOD mice and NOD mice

作　　者：郭彬彬[1] 张梦军[2] 任小珊[3] 舒驰[4] 陈晓玲[4] 邬于川[1] 王莉[4] 

机构地区：[1]泸州医学院免疫学教研室,646000 [2]第三军医大学药学院药物分析与分析化学教研室,重庆400038 [3]重庆大学化学化工学院,400044 [4]第三军医大学基础部免疫教研室,重庆400038

出　　处：《免疫学杂志》2015年第2期93-99,共7页Immunological Journal

基　　金：国家自然科学基金(31100653)

摘　　要：目的观察分析NOD小鼠和NOD.β2mnullHHD小鼠Ⅰ型糖尿病(Type1 diabetes,T1D)发病情况以及脾T细胞亚群的频率及功能差异,揭示CD4+T和CD8+T细胞亚群在HLA-A*0201转基因NOD小鼠和NOD小鼠的T1D发病中作用的异同。方法采用测量血糖的方法观察2种小鼠的发病情况,采用流式细胞术分析小鼠脾淋巴细胞CD3+CD4+T、CD3+CD8+T细胞亚群频率以及这2群细胞分泌IL-17和IFN-γ频率的差异。结果 NOD.β2mnullHHD小鼠较NOD小鼠发病早且严重;NOD.β2mnullHHD小鼠脾淋巴细胞的CD3+CD4+T细胞亚群显著高于NOD小鼠,NOD.β2mnullHHD小鼠脾淋巴细胞的CD3+CD8+T细胞亚群显著低于NOD小鼠;2种小鼠的脾淋巴细胞中CD3+CD4+IL-17+T细胞亚群与CD3+CD8+IL17+T细胞频率无差异;NOD.β2mnullHHD小鼠脾淋巴细胞的CD3+CD4+IFN-γ+T和CD3+CD8+IFN-γ+T细胞亚群频率显著高于NOD小鼠。结论 HLA-2.1分子转入NOD小鼠后HLA-2.1分子加速了HLA-A*0201转基因NOD小鼠T1D的发病进程;NOD.β2mnullHHD小鼠相对NOD小鼠的T1D发病更早、病情更重,这与CD3+CD4+T和CD3+CD8+T细胞分泌的IFN-γ显著相关,而与IL-17无关,为T1D防治的临床转化基础研究提供实验数据。To reveal the different roles of splenic CD4^＋T and CD8^＋T cells in the development of type 1 diabetes（T1D） in humanized NOD mice（NOD.β2m^null HHD mice） and NOD mice,we observed the incidence of T1 D and the frequencies and cytokine secretion of splenic CD4^＋T and CD8^＋T cell subsets in NOD.β2m^null HHD mice and NOD mice. The incidence of T1 D of NOD.β2m^null HHD mice and NOD mice was monitored by blood glucose,and the frequencies of splenic CD4^＋T and CD8^＋T cells and their IL-17/IFN-γ secretion were evaluated by flow cytometry.Compared with NOD mice,the development of T1 D was accelerated and the incidence of T1 D was significantly increased in NOD.β2m^null HHD mice. The frequency of splenic CD3^＋CD4^＋T cells,CD3^＋CD4^＋IFN-γ^＋T and CD3^＋CD8^＋IFN-γ^＋T cells of NOD.βnull2m HHD mice was apparently higher than those of NOD mice. Whereas the frequencies of the splenic CD3^＋CD8^＋T cells of NOD.β2m^null HHD mice were significantly lower than those of NOD mice. However,the frequencies of CD3^＋CD4^＋IL-17^＋T and CD3^＋CD8^＋IL-17^＋T cells showed no significant difference between NOD.β2m^null HHD mice and NOD mice. These results demonstrated that the transgenic expression of HLA-A2.1 moleculesin NOD mice led to acceleration of T1 D,which obviously associates with IFN-γ secreted by splenic CD3^＋CD4^＋T and CD3^＋CD8^＋T cells,but dose not related with IL-17 secretion. Our experimental data would be helpful to the clinical studies of the prevention of T1 D.

关 键 词：HLA-A2.1 NOD.β2m^nullHHD小鼠 INF-γ IL-17 

分 类 号：R587.1[医药卫生—内分泌]