HIV-1慢性感染者CD8^+Tscm异常免疫活化对T细胞耗竭的影响

Effect of abnormal immune activation of CD8^+Tscm on T cell exhaustion in chronically HIV-1 infected patients

目的探讨HIV-1慢性感染者CD8^+干细胞样记忆性T细胞(stem memory T cell,Tscm)免疫活化水平的变化特点及其活化对CD8^+T细胞功能耗竭的影响。方法选取24例未经治疗的HIV-1慢性期感染者和41名健康对照者,采用流式细胞术分别检测健康对照者和HIV-1感染者CD8^+Tscm的比例、CD8^+Tscm的免疫活化水平、CD8^+T细胞表面抑制性分子(CD160、PD-1、TIGIT、TIM-3和LAG-3)表达水平及CD8^+T细胞功能(分泌细胞因子IL-2、IFN-γ和TNF-α的能力);分析CD8^+Tscm的免疫活化水平与CD8^+T细胞抑制性分子表达及CD8^+T细胞功能的相关性。结果与健康对照者相比,HIV-1慢性期感染者CD8^+Tscm的比例显著下降,CD8^+Tscm免疫活化水平(CD38^+HLA-DR^+CD8^+Tscm比例)显著升高。HIV-1慢性期感染者CD8^+Tscm免疫活化水平与CD8^+T细胞分泌IL-2和TNF-α水平呈负相关。HIV-1慢性感染引起CD8^+T细胞抑制性分子(CD160、PD-1、TIGIT和LAG-3)上调,但活化的CD8^+Tscm仅与CD8^+T细胞抑制性分子TIGIT表达水平呈正相关。CD8^+T细胞抑制性分子TIGIT表达水平与CD8^+T细胞分泌IL-2和TNF-α水平呈负相关。结论 HIV-1慢性感染引起CD8^+Tscm的异常免疫活化,活化的CD8^+Tscm通过上调CD8^+T细胞抑制性分子TIGIT抑制CD8^+T细胞功能。

Objective To investigate the level of CD8＋ stem memory T cell （Tscm） immune activation and its effect on CD8＋ T cell exhaustion in chronically HIV-1 infected patients. Methods Twenty-four treatment-naive HIV-1 chronically infected patients and 41 healthy controls were selected in this study. Flow cytometry was performed to detect the percentage of CD8＋Tscm in chronically HIV- 1 infected patients and healthy controls. The level of immune inhibitory molecules （CD160, PD-l, TIGIT, TIM-3 and LAG-3） on CD8＋T cells and the ability of cytokine secretion （IL-2, IFN-γ and TNF-α） by CD8＋T cells were also measured in each subject. Correlation analysis was used to demonstrate the relation-ship between the level of immune activation of CD8＋Tscm and the expression level of immune inhibitory molecules or the level of cytokine secretion by CD8＋T cells. Results Compared with healthy controls, the proportion of CD8＋Tscm in chronically HIV- 1 infected patients was significantly decreased. The level of CD8＋Tscm immune activation （the percentage of CD38＋HLA-DR＋CD8＋Tscm） was much higher than that of healthy controls. The level of CD8＋Tscm immune activation was negatively correlated with the percentage of IL-2 or TNF-α secreting CD8＋T cells in chronically HIV- 1 infected patients. The expression level of immune inhibitory molecules （CD 160, PD-1, TIGIT and LAG-3） on CD8＋T cells were upregulated after HIV- 1 infection, however, only the level of TIGIT on CD8＋T cells had a positive correlation with the level of CD8＋Tscm activation. Moreover, the level of TIGIT on CD8＋T cells was negatively correlated with the percentage of IL- 2 or TNF-α secreting CD8＋T cells. Conclusion Abnormal immune activation on CD8＋Tscm occurres during HIV- 1 chronic infection stage. Impaired CD8＋T cell function is induced by the high level of CDS＋Tscm immune activation through the up-regulation of TIGIT expression on CD8＋T cells.