CD11b^+ NKT细胞抑制Poly I:C诱导小鼠肝损伤中CD8^+T细胞增殖反应  

Effects of CD11b^+ NKT cells derived from poly-I:C-challenged mice on CD8^+T cell proliferation and cytotoxicity

作　　者：刘音[1] 陈朱波[1] 韩岩梅[2] 

机构地区：[1]中国医学科学院基础医学研究所免疫学系,医学分子生物学国家重点实验室,北京100005 [2]第二军医大学免疫学研究所医学免疫学国家重点实验室,上海200433

出　　处：《中国肿瘤生物治疗杂志》2014年第5期493-498,共6页Chinese Journal of Cancer Biotherapy

基　　金：国家(重点)实验室专项经费资助(No.2060204)~~

摘　　要：目的:研究Poly I:C诱导的肝损伤模型中肝脏内上调的CD11b+NKT细胞对CD8+T细胞增殖反应的作用。方法:经腹腔注射Poly I:C(20μg/g)制备Poly I:C诱导小鼠肝损伤模型,流式细胞术检测CD11b+NKT细胞的比例、T细胞增殖反应和CD8+T细胞的杀伤功能,ELISA法检测细胞培养上清中的细胞因子浓度。结果:Poly I:C诱导的肝损伤模型小鼠的肝脏中CD11b+NKT细胞的比例显著上升[(71.7±5.3)%vs(12.4±3.6)%,P<0.01]。细胞因子表达谱分析发现,CD11b+NKT细胞分泌IFN-γ、IL-4和IL-10的能力显著低于CD11b-NKT细胞。功能分析发现,CD11b+NKT细胞能够显著抑制anti-CD3/CD28单抗诱导非特异性的和OVA特异性的CD8+T细胞增殖反应,而CD11b-NKT细胞没有此抑制功能;进一步分析发现,CD11b+NKT细胞并不影响CD8+T细胞的杀伤功能。结论:Poly I:C诱导的肝损伤模型小鼠肝脏中CD11b+NKT细胞比例升高,该细胞能够负反馈抑制CD8+T细胞的增殖反应,但是并不影响CD8+T细胞的杀伤功能。Objective： To investigate the effect of expanded CD11b^＋NKT cells isolated from the injured murine liver following poly-I： C challenge on the proliferation and function of normal murine CD8^＋T cells in vitro. Methods： Male C57 BL /6 mice were treated with poly-I： C at 20 μg /g. CD11b^＋and CD11b^-NKT cells were isolated from the liver 24 h after poly-I： C- treatment. CD8^＋T cells were isolated from normal male OT-I mice and co-cultured with the isolated hepatic CD11b^＋and CD11b^-NKT cells,respectively. The proliferation and cytotoxic ability of CD8^＋T cells in the coculture were both assessed by flow cytometry. The concentration of major immunoregulatory cytokines was determined by ELISA. Results： Poly-I： C treatment significantly increased the proportion of CD11b^＋NKT cells in the liver. After stimulation,CD11b^＋hepatic NKT cells produced less IFN-γ,IL-4 and IL-10 than CD11b^-hepatic NKT cells. CD11b^＋hepatic NKT cells significantly inhibited both antigen-specific and nonspecific immune responses of CD8^＋T cells,while CD11b^-hepatic NKT cells showed no inhibitory effect. CD11b^＋hepatic NKT cells did not significantly alter the cytotoxic ability of activated CD8^＋T cells. Conclusion： Poly-I： C-nduced liver injury is associated with the expansion of CD11b^＋hepatic NKT cells. While these CD11b^＋hepatic NKT cells have little effect on the cytotoxic activity of activated CD8^＋T cells,they significantly inhibit CD8^＋T cell proliferation.

关 键 词：NKT细胞 CD11B CD8^+T细胞 免疫调节 肝损伤 Poly I:C 

分 类 号：R735.7[医药卫生—肿瘤] R730.2[医药卫生—临床医学]