HIV/AIDS患者B7-H1的表达特点及与疾病进展关系研究

摘要

Objective To investigate the level of B7-H1 and its counter-receptor PD-1 expression in mDC and different subsets of T lymphocytes in HIV infected individuals in China and to analyze the correlation between the level of B7-H1/PD-1 and disease progression, and to demonstrate that PD-1/PD-L1-dependent inhibition is operating in HIV infected patients.Methods Percentage of B7-H1 and PD-1 expression in mDC, CD+4 T cells and CD+8 T cells from thirty-six untreated HIV infected patients and 20 health controls were selected and detected by flow-cytometry, its correlations with CD+4 T cell absolute counts and plasma viral loads were analyzed.Results The percentage of B7-H1 expression in mDC, CD+4 T cells and CD+8 T cells (mean 15.21, mean 20.63, mean 13.5)were higher than that of health controls (all P<0.05).The percentage of PD-1 expression in CD+4 T cells and CD+8 T cells (mean 17.91, mean 19.21)were higher than that of health controls (P<0.05, P<0.05). The level of B7-H1 and PD-1 expression were inversely correlated with CD+4 T-cell counts(mDC+B7-H1+:r=-0.647, P<0.01;CD+4B7-H1+:r=-0.489, P=0.002;CD+8B7-H1+:r=-0.372, P=0.026;CD+4PD-1+:r=-0.374, P=0.025;CD+8PD-1+:r=-0.455, P=0.005) and positively correlated with HIV viral load(mDC+B7-H1+:r=0.662, P<0.01;CD+4B7-H1+: r=0.426, P=0.01;CD+8B7-H1+:r=0.531, P=0.001;CD+4PD-1+:r=0.362, P=0.03;CD+8PD-1+:r=0.380, P=0.022).Conclusion The level of B7-H1 and PD-1 expression was associated with HIV disease progression, which provides a useful marker to define disease progression of HIV infection.%目的 研究HIV/AIDS患者外周血mDC及不同亚群T淋巴细胞B7-H1及PD-1的表达水平,分析其与疾病进展的相关性,探讨B7-H1及PD-1信号通路在HIV感染中的作用.方法 采集中国医科大学附属第一医院艾滋病研究所红丝带门诊36例未经抗病毒治疗的HIV/AIDS患者(无症状HIV组、AIDS组)及20名健康对照组抗凝全血,用流式细胞仪检测外周血mDC及不同亚群T淋巴细胞表面B7-H1及配体PD-1的表达水平,并分析其与疾病进展的相关性.结果 中国HIV/AIDS患者外周血mDC、CD+4T淋巴细胞和CD+8T淋巴细胞表面B7-H1表达水平(均值分别为15.21、20.63、13.5)显著高于健康对照组(平均值分别为0.38、4.91、3.26),配体PD-1在CD+4T淋巴细胞和CD+8T淋巴细胞表达水平(平均值分别为17.91、19.21)显著高于健康对照组(均值分别为10.6、8.71).HIV/AIDS患者B7-H1及配体表达水平与CD+4T淋巴细胞数量显著负相关(mDC+B7-H1+:r=-0.647,P<0.01;CD+4B7-H1+:r=-0.489,P=0.002;CD+8B7-H1+:r=-0.372,P=0.026;CD+4PD-1+:r=-0.374,P=0.025;CD+8PD-1+:r=-0.455,P=0.005),与病毒载量(平均2.9E+06)显著正相关(mDC+B7-H1+:r=0.662,P<0.01;CD+4B7-H1+:r=0.426,P=0.01;CD+8B7-H1+:r=0.531,P=0.001;CD+4PD-1+:r=0.362,P=0.03;CD+8PD-1+:r=0.380,P=0.022).结论 HIV/AIDS患者不同病程外周血mDC、CD+4T淋巴细胞、CD+8T淋巴细胞B7-H1及配体表达水平显著升高,与疾病进展密切相关,高水平共刺激信号通路B7-H1/PD-1可能为导致疾病进展的原因之一.