TIGIT信号在日本血吸虫感染小鼠Th1/Th2反应平衡中的作用研究

Study on role of TIGIT signal in Th1/Th2 balance in Schistosoma japonicum-infected mice

目的研究TIGIT信号在日本血吸虫感染过程中Th1/Th2反应平衡中的作用。方法 C57BL/6小鼠感染日本血吸虫尾蚴,并以未感染小鼠作为正常对照。感染0、3、5、8、13周时取小鼠脾脏,采用流式细胞术检测小鼠脾脏淋巴细胞中TIGIT阳性细胞比例,以及TIGIT阴性和TIGIT阳性细胞上Ki67、IFN.γ、IL.4表达水平。结果日本血吸虫感染组小鼠脾脏中TIGIT+细胞占CD4+T细胞的比例显著高于正常对照组(29.30%±0.70%vs.3.09%±0.50%;t=29.09,P<0.01),但感染组和对照组小鼠脾脏中TIGIT+细胞占CD8+T细胞的比例差异无统计学意义(3.61%±0.26%vs.3.58%±0.16%;t=0.108,P>0.05),且感染组和对照组小鼠脾脏中TIGIT+细胞占非T细胞的比例差异亦无统计学意义(1.86%±0.19%vs.1.37%±0.17%;t=1.931,P>0.05)。进一步分析发现,Ki67在TIGIT+细胞上的表达比例(17.03%±0.64%)较其在TIGIT.细胞上表达的比例(6.59%±0.37%)显著升高(t=14.09,P<0.01),而CD4+TIGIT+细胞中Th2/Th1比值显著高于CD4+TIGIT.细胞(39.28%±3.75%vs.11.79%±1.64%;t=6.721,P<0.01)。结论感染日本血吸虫后,CD4+T细胞上TIGIT表达增加,且可能通过诱导Th2细胞增殖进而促进Th2细胞比例增加。

Objective To investigate the role of TIGIT signal in Th1/Th2 balance in the process of Schistosoma japonicum infection.Methods Male C57 BL/6 mice were infected with cercariae of S. japonicum,and normal uninfected mice served as the controls. The percentages of TIGIT＋cells,Ki67~＋CD3~＋CD4~＋TIGIT＋cells,Ki67~＋CD3~＋CD4~＋TIGIT-cells,IFN-γ＋CD3＋CD4＋TIGIT＋cells,IFN-γ＋CD3＋CD4＋TIGIT-cells,IL-4~＋CD3~＋CD4~＋TIGIT＋cells and IL-4~＋CD3~＋CD4~＋TIGIT-cells were evaluated in mouse spleen by flow cytometry.Results The proportion of TIGIT~＋CD4~＋T cells was higher in the spleen of S. japonicum-infected mice than in the normal uninfected mice（29.30%±0.70% vs. 3.09%±0.50%;t = 8.834,P〈 0.01）. However,no significant difference in the percentages of TIGIT＋CD8＋T cells between the infection group and normal controls（3.61%±0.26% vs. 3.58%±0.16%;t = 0.108,P〉 0.05）,and no significant difference was detected in the percentages of TIGIT＋cells in non-T cells between the infection group and controls（1.86%±0.19% vs.1.37%±0.17%;t = 1.931,P 〉0.05）. In addition,the proportion of Ki67 in the TIGIT＋cells was higher than that in the TIGIT-cells（17.03%±0.64% vs. 6.59%±0.37%;t = 14.09,P 〈0.01）. The Th2/Th1 ratio was higher in the TIGIT~＋CD4~＋T cells than in the TIGIT-CD4~＋T cells（39.28%±3.75% vs. 11.79%±1.64%;t =6.721,P 〈0.01）.Conclusion The TIGIT signaling may be involved in the development of Th2 responses in the mice infected with S. japonicum.