雌性和雄性非肥胖糖尿病小鼠中CD8^(+)T细胞分化亚群差异研究  

Characterization of CD8^(+)T cell subsets in male and female non-obese diabetic mice

作　　者：杨数数 刘东[1] 黎婕 张梦军[2] 王莉[1] YANG Shushu;LIU Dong;LI Jie;ZHANG Mengjun;WANG Li(Department of Immunology,College of Basic Medical Sciences,Faculty of Pharmacy and Laboratory Medicine,Army Medical University(Third Military Medical University),Chongqing,400038,China;Department of Pharmaceutical Analysis,Faculty of Pharmacy and Laboratory Medicine,Army Medical University(Third Military Medical University),Chongqing,400038,China)

机构地区：[1]陆军军医大学(第三军医大学):基础医学院免疫学教研室,重庆400038 [2]陆军军医大学(第三军医大学)药学与检验医学系药物分析学教研室,重庆400038

出　　处：《陆军军医大学学报》2024年第8期837-848,共12页Journal of Army Medical University

基　　金：国家自然科学基金面上项目(82071825,81871301)。

摘　　要：目的以雌性和雄性非肥胖糖尿病(nonobese diabetic,NOD)小鼠以及健康对照癌症研究所(institute for cancer research,ICR)小鼠为研究对象,比较分析初始、效应、记忆、耗竭以及调节性CD8^(+)T细胞分化亚群差异,探讨1型糖尿病(type 1 diabetes,T1D)背景下的性别因素对CD8^(+)T细胞分化命运的影响。方法采用流式细胞术检测雌雄NOD小鼠脾脏、胰腺引流淋巴结(pancreatic draining lymph nodes,pLN)、胰腺浸润淋巴细胞(pancreas-infiltrating lymphocytes,PIL)、初始T细胞(naive T cells,T_(N))、中枢记忆T细胞(central memory T cells,T_(CM))、效应T细胞(effector T cells,T_(EFF))、效应前体样T细胞(effector precursor T cells,T_(EP))、耗竭T细胞(exhausted T cells,T_(EX))、耗竭前体T细胞(precursor exhausted T cells,T_(PEX))以及调节性T细胞(regulatory T cells,Tregs)等CD8^(+)T细胞分化亚群的频率和表型差异。结果与雄性NOD小鼠比较,雌性NOD小鼠pLN及PIL中IFN-γ^(+)、CD107a^(+)和CCL5^(+)CD8^(+)T_(EFF)频率显著升高(P<0.01,P<0.05,P<0.05),同时脾脏中CD8^(+)T_(N)、CD8^(+)T_(CM)、CD8^(+)T_(EX)、CD8^(+)T_(PEX)和CD122^(+)CD8^(+)Tregs亚群的频率均显著降低(P<0.01,P<0.01,P<0.01,P<0.01,P<0.001);而雌性和雄性ICR小鼠体内除CD122^(+)CD8^(+)Tregs差异变化与NOD小鼠一致(P<0.05),其余上述各CD8^(+)T细胞分化亚群无显著差异。结论雄激素可能通过抑制记忆T细胞向效应T细胞分化,同时促进效应T细胞功能耗竭,导致雌雄发病率差异。Objective To compare and analyze the differences in CD8^(+)naive,effector,memory,exhausted and regulatory T cells in order to investigate the impact of gender on the differentiation fate of CD8^(+)T cells in the context of type 1 diabetes(T1D)based on female and male non-obese diabetic(NOD)mice and healthy Institute for Cancer Research(ICR)mice.Methods The frequencies and phenotypes of CD8^(+)T cell differentiation subsets including naive T cells(T_(N)),central memory T cells(T_(CM)),effector T cells(T_(EFF)),effector precursor T cells(T_(EP)),exhausted T cells(T_(EX)),precursor exhausted T cells(T_(PEX))and regulatory T cells(Tregs)in the spleen,pancreatic draining lymph nodes(pLN)and pancreas infiltrating lymphocytes(PIL)of male and female NOD mice were detected by flow cytometry.Results The frequencies of IFN-γ^(+),CD107a^(+)and CCL5^(+)CD8^(+)T_(EFF)in pLN and PIL of female NOD mice were significantly higher than those of male NOD mice.However,the frequencies of CD8^(+)T_(N),CD8^(+)T_(CM),CD8^(+)T_(EX),CD8^(+)T_(PEX)and CD122^(+)CD8^(+)Tregs subsets in the spleen were significantly decreased.While there were no significant differences in the above CD8^(+)T cell subsets except CD8^(+)Tregs between female and male ICR mice.Conclusion Androgen may inhibit the differentiation of memory T cells into effector T cells and promote the exhaustion of effector T cells,leading to the difference in morbidity between the male and female mice.

关 键 词：1型糖尿病 CD8^(+)T淋巴细胞 调节性T细胞 耗竭T细胞 初始T细胞 记忆T细胞 

分 类 号：R339.2[医药卫生—人体生理学] R392.12[医药卫生—基础医学] R587.1