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（20 μg/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 C57BL/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 co-culture 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.

国家（重点）实验室专项经费资助（No. 2060204）