HIV-1感染过程中CD8^+T细胞PD-1水平增高与其活化状态正相关  

Upregulated PD-1 on CD8^+T cells is positively correlated with activation of T cells during HIV-1 infection

作　　者：肖健[1,2] 刘显 郁晓磊 董原[2] 王绪琴[2] 冷静 杨荣阁[3] 王盈[2] XIAO Jian LIU Xian YU Xiaolei DONG Yuan WANG Xuqin LENG Jing YANG Rongge WANG Ying(GuangxJ Key Laboratory for Complementary and Alternative Medicine Experimental Animal Models, Nanning 530001 Shanghai Center for Disease Control and Prevention, Shanghai 200336 Wuhan Institute of Virology, Chinese Academy of Science, Wuhan 430071, China)

机构地区：[1]广西特色实验动物病证模型重点实验室,广西南宁530001 [2]上海市疾病预防控制中心,上海200336 [3]中国科学院武汉病毒研究所,湖北武汉430071

出　　处：《细胞与分子免疫学杂志》2016年第10期1372-1377,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家科技重大专项"十二五"项目(2012ZX10001006-003-007);国家自然科学基金(81260463);广西自然科学基金(2012-GXNSFAA-053120);病毒学国家重点实验室开放研究基金(2015IOV004);广西中医药大学重点课题(ZD2012002)

摘　　要：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 investigate the expressions of programmed death-1（ PD-1）,CD38,human leukocyte antigen DR（ HLA-DR） and anligen KI-67（ ki67） on CD8^＋T cel s,and the correlation between PD-1 / PD-L1 pathway and activation,immunodepletion during HIV-1 infection. Methods Peripheral blood mononuclear cel s were isolated by density gradient centrifugation from 87 HIV-1 patients and 22 healthy controls. The expression levels of PD-1,CD38,HLA-DR and ki67 on CD8^＋T cells were detected by flow cytometry. Furthermore,we evaluated the production of interferon-γ（ IFN-γ） and tumor necrosis factor α（ TNF-α） in CD8^＋T cells by blocking PD-1 / PD-L1 pathway in the presence of PD-L1 m Ab. Results Compared with healthy controls,HIV-1 infection resulted in a significant increase in PD-1 expression on CD8^＋T cells. Correlation analysis showed that PD-1 expression on CD8^＋T cell was positively associated with HIV-1 viral loading（ VL） and negatively associated with the number of CD4^＋T cells. Furthermore,PD-1 expression was positively correlated with CD38 and HLA-DR expressions on CD8^＋T cells in HIV-1 infected patients. There was no association between PD-1 and ki67 expression on CD8^＋T cells in HIV-1 infected patients. Blockage of the PD-1 / PD-L1 pathway increased TNF-α and IFN-γ production in CD8^＋T cells. Conclusion PD-1 expression on CD8^＋T cells is significantly upregulated during HIV-1 infection. PD-1expression is correlated with CD8^＋T cell inhibition,immunodepletion and disease progression. Moreover,the blockage of PD-1 / PD-L1 pathway can restore the function of CD8^＋T cells in HIV-1 patients.

关 键 词：人类免疫缺陷病毒1型(HIV-1) CD8+T细胞 细胞程序性死亡蛋白1(PD-1) 免疫活化 免疫耗竭 

分 类 号：R392.12[医药卫生—免疫学] R446.63[医药卫生—基础医学]