长期抗病毒治疗HIV-1感染者T细胞的线粒体氧化磷酸化特点  

The characteristics of mitochondrial oxidative phosphorylation of T cells in antiretroviral treated HIV-infected individuals

作　　者：万林钰 沈莉丽 曹文静 张超 范兴 宋锦文 王福生 WAN Linyu;SHEN Lili;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 PL A General Hospital,National Clinical Research Center for Infectious Diseases,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国家感染性疾病临床医学研究中心,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》2022年第2期138-143,共6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);国家“十三五”重大专项(2018ZX10302104-002-001)。

摘　　要：目的分析长期抗病毒治疗的HIV-1感染者T淋巴细胞中线粒体质量和氧化磷酸化水平,探讨其与主要临床指标的关系及临床意义。方法本研究入组20例健康对照(HCs)和67例ART时间大于2年的HIV-1感染者,其中完全免疫应答者(CRs)29例,免疫无应答者(INRs)38例。通过流式细胞术检测CD4、CD8细胞线粒体质量和氧化磷酸化水平,分析线粒体质量和氧化磷酸化水平与CD4、CD8细胞计数、以及CD4/CD8细胞比值的关系。结果HCs、CRs、INRs三组间T细胞线粒体质量差异无统计学意义;与HCs和CRs组相比,INRs组CD4和CD8细胞线粒体氧化磷酸化水平明显升高。长期ART的HIV-1感染者中,CD4细胞线粒体氧化磷酸化水平与CD4细胞计数(r=-0.3807,P=0.0015)、CD4/CD8细胞比值(r=-0.3385,P=0.0051)、基线CD4细胞计数负相关(r=-0.3005,P=0.0135);CD8细胞线粒体氧化磷酸化水平与CD4细胞计数(r=-0.3667,P=0.0023)、CD4/CD8细胞比值(r=-0.4429,P=0.0002)、基线CD4细胞计数负相关(r=-0.3293,P=0.0065)。结论免疫无应答者T淋巴细胞线粒体氧化磷酸化水平异常升高,并且线粒体氧化磷酸化水平的升高伴随着CD4细胞计数、CD4/CD8细胞比值的降低,提示T淋巴细胞线粒体功能障碍与HIV-1感染者免疫恢复相关。Objective To explore the association of mitochondrial mass and oxidative phosphorylation of T cells with major clinical indicators in HIV-infected patients receiving long-term antiretroviral therapy(ART)and its clinical significance.Methods Twenty healthy controls(HCs)and 67 patients,including 29 complete responders(CRs)and 38 immunological non-responders(INRs),were enrolled in this study.The mitochondrial mass and oxidative phosphorylation of CD4 and CD8 T cells were detected by flow cytometry.We further analyzed the associations between mitochondrial mass and oxidative phosphorylation with clinical indicators,including CD4 T cell counts,CD8 T cell counts,and CD4/CD8 ratio.Results 1)The mitochondrial mass of T cells did not differ among HCs,CRs,and INRs;While compared with HCs and CRs,the oxidative phosphorylation of CD4 and CD8 T cells was increased in INRs.2)In HIV-infected patients receiving longterm suppressive ART,the oxidative phosphorylation of CD4 T cells was negatively correlated with CD4 T cell counts(r=-0.3807,P=0.0015),CD4/CD8 ratio(r=-0.3385,P=0.0051)and baseline CD4 T cell counts(r=-0.3005,P=0.0135);meanwhile,the oxidative phosphorylation of CD8 T cells was also negatively correlated with CD4 T cell counts(r=-0.3667,P=0.0023),CD4/CD8 ratio(r=-0.4429,P=0.0002)and baseline CD4 T cell counts(r=-0.3293,P=0.0065).Conclusion The mitochondrial dysfunction in INR is manifested by abnormal increased oxidative phosphorylation on T cells.The increase of oxidative phosphorylation is accompanied by the decrease of CD4 T cell counts and CD4/CD8 ratio,suggesting that mitochondrial dysfunction is associated with immune recovery in HIV-infected patients.

关 键 词：艾滋病病毒 免疫无应答者 线粒体氧化磷酸化 T细胞 

分 类 号：R373.9[医药卫生—病原生物学]