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

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.