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目的分析人类免疫缺陷病毒1型(HIV-1)感染者CD8+T细胞程序性死亡蛋白1(PD-1)、CD38、人白细胞抗原DR(HLA-DR)及KI-67抗原(ki67)的表达水平,探讨HIV-1感染过程中CD8~+T细胞PD-1表达水平与免疫活化和免疫耗竭的关系及意义。方法收集HIV-1感染者87例,健康志愿者22例,密度梯度法分离外周血单个核细胞;采用流式细胞术分析其CD8+T细胞PD-1、CD38、HLA-DR、ki67的表达水平;观察用抗PD-L1 m Ab阻断PD-1/PD-L1通路后CD8~+T细胞分泌肿瘤坏死因子α(TNF-α)、γ干扰素(IFN-γ)的水平变化。结果 HIV-1感染者CD8~+T细胞PD-1表达水平显著高于健康对照组;CD8~+T细胞PD-1水平与病毒载量呈正相关,与CD4~+T细胞数呈负相关;CD8~+T细胞PD-1与CD38、HLA-DR表达呈正相关,与ki67表达无相关性;体外阻断PD-1/PD-L1通路后TNF-α、IFN-γ的表达量增加。结论 HIV-1感染者外周血CD8~+T细胞PD-1表达增加;PD-1过表达与HIV感染过程中CD8~+T细胞功能受抑、免疫耗竭及疾病进程相关;体外阻断PD-1/PD-L1通路可恢复CD8~+T细胞功能。
Objective To analyze the expression of CD8 + T-cellprotein 1 (PD-1), CD38, human leukocyte antigen DR (HLA-DR) and KI-67 antigen (ki67) in human immunodeficiency virus type 1 (HIV- To investigate the relationship between PD-1 expression and immune activation and immune depletion in CD8 + T cells during HIV-1 infection. Methods 87 cases of HIV-1 infection, 22 healthy volunteers were collected and peripheral blood mononuclear cells were separated by density gradient. The expressions of PD-1, CD38, HLA-DR and ki67 in CD8 + T cells were analyzed by flow cytometry The levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) secreted by CD8 + T cells after PD-1 / PD-L1 pathway were blocked by anti-PD- Results PD-1 expression in CD8 + T cells of HIV-1 infected patients was significantly higher than that in healthy controls. PD-1 levels of CD8 + T cells were positively correlated with viral load and negatively correlated with CD4 + T cells. The expression of PD-1 and CD38, HLA-DR in CD8 ~ + T cells was positively correlated with ki67 expression, and the expression of TNF-α and IFN-γ in PD-1 / PD-L1 pathway was increased in vitro. Conclusion The expression of PD-1 in peripheral blood CD8 + T cells is increased in HIV-1 infected patients. PD-1 overexpression is associated with suppressed CD8 + T cell function, immune depletion and disease progression during HIV infection. PD- 1 / PD-L1 pathway can restore CD8 ~ + T cell function.