经治HIV-1感染者CD8细胞免疫紊乱与CXCL9/10/11的相关性分析  

The relationship of CD8+T cell differentiation and activation with chemokine CXCL9/10/11 in ART-treated HIV-1 infected patients

作　　者：沈莉丽 万林钰 曹文静 张超 范兴 宋锦文 王福生 SHEN Lili;WAN Linyu;CAO Wenjing;ZHANG Chao;FAN Xing;SONG Jinwen;WANG Fusheng(Bengbu Medical College,Bengbu 233000,Anhui,China;Senior Department of Infectious Diseases,the Fifth Medical Center of PLA General Hospital,Beijing 100039;The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,Anhui)

机构地区：[1]蚌埠医学院,安徽蚌埠233000 [2]中国人民解放军总医院第五医学中心感染病医学部,北京100039 [3]中国科学技术大学生命科学与医学部中国科学技术大学附属第一医院,合肥230001

出　　处：《中国艾滋病性病》2023年第3期251-257,共7页Chinese Journal of Aids & STD

基　　金：国家自然科学基金青年科学基金项目(82101837,81901617);中国科协军事科技领域青年人才托举工程(2020-JCJQQT-034);北京市自然科学基金面上项目(7222171)。

摘　　要：目的分析经治HIV-1感染者CD8细胞分化及激活特征,探索其与趋化因子CXCL9/10/11及CD4/CD8细胞比值的关系。方法入组33例ART时间大于2年且血浆VL小于20拷贝/mL的HIV-1感染者以及15例健康对照,通过流式细胞术检测CD8细胞分化和激活水平,利用酶联免疫吸附法检测血浆CXCL9/10/11水平,随后分析CD8细胞分化、激活水平和血浆CXCL9/10/11水平以及CD4/CD8细胞比值的相关性。结果与健康对照相比,经治HIV-1感染者幼稚CD8细胞占比(中位数9.6%vs.28.6%,P=0.004)显著降低,而效应记忆CD8细胞占比(中位数36.9%vs.7.0%,P<0.0001)及HLA-DR+CD38+CD8细胞占比(中位数7.4%vs.3.3%,P<0.0001)显著升高。在经治HIV-1感染者中,HLA-DR+CD38+CD8细胞占比与CXCL9(r=0.477,P=0.005)和CXCL11(r=0.4029,P=0.0201)水平显著正相关,效应CD8细胞占比与CXCL9(r=0.5819,P=0.0004)、CXCL10(r=0.4168,P=0.0158)水平显著正相关,而幼稚CD8细胞占比与CXCL9(r=-0.4493,P=0.0087)、CXCL10(r=-0.4487,P=0.0088)水平显著负相关。此外,经治HIV-1感染者效应CD8细胞占比与CD4/CD8细胞比值显著负相关(r=-0.4018,P=0.0205)。结论长期接受ART的HIV-1感染者CD8细胞仍处于异常激活及过度分化状态。趋化因子CXCL9/10/11的分泌可能影响CD8细胞激活、效应CD8细胞扩增以及幼稚CD8细胞和CD4/CD8细胞比值恢复。Objective To explore the characteristics of CD8+T cell differentiation and activation and their relationships with levels of chemokine CXCL9/10/11.Methods 33 HIV-1 infected patients who had received ART for over two years with plasma VL below 20 copies/m L and 15 healthy controls were recruited in this study.CD8+T cell differentiation and activation were detected by flow cytometry,and levels of chemokine CXCL9/10/11 were detected by enzyme-linked immunosorbent assay.We further analyzed the correlations among CD8+T cell differentiation,activation,chemokine CXCL9/10/11 and CD4/CD8 ratio.Results Compared with healthy controls,the proportion of na?ve CD8+T cells(median 9.6%vs.28.6%,P=0.004)decreased significantly,but proportions of effector memory CD8+T cells(median36.9%vs.7.0%,P<0.0001)and HLA-DR+CD38+CD8+T cells(median 7.4%vs.3.3%,P<0.0001)increased significantly in ART-treated HIV-1 infected patients.In ART-treated HIV-1 infected patients,the proportion ofHLA-DR+CD38+CD8+T cells was positively correlated with levels of CXCL9(r=0.477,P=0.005)and CXCL11(r=0.4029,P=0.0201),the proportion of effector CD8+T cells was positively correlated with levels of CXCL9(r=0.5819,P=0.0004)and CXCL10(r=0.4168,P=0.0158),and the proportion of na?ve CD8+T cells was negatively correlated with levels of CXCL9(r=-0.4493,P=0.0087)and CXCL10(r=-0.4487,P=0.0088).Furthermore,the proportion of effector CD8+T cells was negatively correlated with CD4/CD8 ratio in ART-treated HIV-1 infected patients(r=-0.4018,P=0.0205).Conclusions Residual CD8+T cell activation and skewed CD8+T cell differentiation still exist in ART-treated HIV-1 infected patients.The chemokine CXCL9/10/11 may impact CD8+T cell activation,effector CD8+T cell proliferation,and na?ve CD8+T cell and CD4/CD8 ratio recovery.

关 键 词：1型艾滋病病毒 抗反转录病毒治疗 CD8细胞分化 CD8细胞激活 CXCL9 CXCL10 

分 类 号：R373.9[医药卫生—病原生物学]