NOD小鼠人源化后CD4~＋ Tregs和CD8~＋ Tregs频率和功能变化及意义  

The difference and significance of the function and frequencies of CD4^+ Tregs and CD8^+ Tregs in humanized NOD mice and NOD mice

作　　者：张梦军[1] 韩清娟[1] 陈晓玲 陈禹彤 王莉 

机构地区：[1]陆军军医大学(第三军医大学)药学系药物分析与分析化学教研室,400038 [2]陆军军医大学基础部全军免疫学研究所,400038 [3]陆军军医大学学员旅二营,400038

出　　处：《免疫学杂志》2018年第1期19-26,共8页Immunological Journal

基　　金：国家自然科学基金(31771002,31570931);大学生创新创业训练计划(201790031010)

摘　　要：目的观察NOD小鼠人源化后,CD4^+和CD8^+调节性T细胞(regulatory T cells,Tregs)频率和功能的变化,揭示Tregs在人源化NOD小鼠1型糖尿病中的作用及免疫学机制可能的变化。方法流式细胞术分别分析12周龄未发病的人源化NOD小鼠和NOD小鼠脾淋巴细胞和胰腺淋巴结细胞中CD8^+CD122^+T、CD8^+CD28-T、CD8^+CD25^+Foxp3^+T和CD4^+CD25^+Foxp3^+T细胞的频率,并采用3H-Td R掺入法检测脾CD4^+CD25^+T和CD8^+CD25^+T细胞的免疫抑制功能。结果人源化NOD小鼠和NOD小鼠的脾淋巴细胞和胰腺淋巴结细胞中CD4^+CD25^+Foxp3^+T细胞频率无显著性差异(P>0.05),而人源化NOD小鼠脾淋巴细胞和胰腺淋巴结细胞中CD8^+CD122^+T、CD8^+CD28-T、CD8^+CD25^+Foxp3^+T细胞等CD8^+Tregs亚群的频率较NOD小鼠都显著降低,但NOD小鼠人源化后,CD4^+CD25^+T和CD8^+CD25^+T细胞的免疫抑制功能并没有显著性差异;同时与人源化NOD小鼠相比,NOD小鼠的胰腺淋巴结细胞中CD8^+T细胞频率更低。结论人源化NOD小鼠脾脏和胰腺淋巴结中CD8^+Tregs亚群频率的降低,引起其胰腺淋巴结中CD8^+T细胞频率的升高,导致胰岛β细胞破坏更严重,可能是引起人源化NOD小鼠自发1型糖尿病较NOD小鼠明显提前且加重的因素之一。In order to reveal the difference of splenic CD4＋ Tregs and CD8＋ Tregs in the diabetes development between humanized NOD mice and NOD mice, we observed the frequencies of CD8＋CD122＋ T, CD8＋CD28-T, CD8＋ CD25＋Foxp3＋ T and CD4＋CD25＋Foxp3＋ T ceils in spleen and pancreatic lymph nodes from humanized NOD mice and NOD mice. The frequencies of CD4＋ Tregs and CD8＋ Tregs were evaluated by flow cytometry. Data showed that there was no significant difference in the frequency of CD4＋CD25＋Foxp3＋ T cells in spleen and pancreatic lymph nodes between humanized NOD mice and NOD mice. Whereas the frequencies of the CD8＋CD122＋ T, CD8＋CD28- T, and CD8＋CD25＋Foxp3＋ T cells in spleen and pancreatic lymph nodes from humanized NOD mice were significantly lower than those of NOD mice. Furthermore, splenic CD4＋CD25＋T and CD8＋CD25＋ T cells from both humanized NOD mice and NOD mice significantly inhibited the proliferation of their CD4＋CD25- T cells. Our experiment result indicated that the lower frequencies of CD8＋ Tregs in spleen and pancreatic lymph nodes and the higher frequencies of CD8＋ T cells in pancreatic lymph nodes of humanized NOD mice might be associated with acceleration of type 1 diabetes in humanized NOD mice. These results would be helpful to the studies of clinical transformation for the prevention of type 1 diabetes.

关 键 词：1型糖尿病 人源化NOD小鼠 CD4^+ TREGS CD8^+ TREGS 

分 类 号：R392.6[医药卫生—免疫学]