HIV-1感染者血浆丙酮酸对CD8^(+)T细胞功能的影响及临床意义  

The impact and clinical significance of plasma pyruvate on CD8^(+)T cell function in people living with HIV-1

作　　者：王酉源 胡伟 张超 王福生 WANG Youyuan;HU Wei;ZHANG Chao;WANG Fusheng(Medical School of Chinese PLA,Beijing 100853,China;National Clinical Research Center for Infectious Diseases,Fifth Medical Center of Chinese PLA General Hospital,Beijing 100039,China)

机构地区：[1]解放军医学院,北京100853 [2]解放军总医院第五医学中心国家感染性疾病临床研究中心,北京100039 [3]解放军总医院急诊科,北京100039

出　　处：《传染病信息》2023年第2期97-102,113,共7页Infectious Disease Information

基　　金：国家科技重大专项(2018ZX10302104-002);国家创新群体项目(413FZT)。

摘　　要：目的探讨HIV-1感染者血浆丙酮酸对CD8^(+)T细胞功能的影响与疾病进展的关系。方法入组11例健康对照(healthy controls,HCs)与55例接受长期抗逆转录病毒治疗的HIV-1感染者。通过液相色谱质谱联用法检测HCs与HIV-1感染者血浆丙酮酸水平,比较丙酮酸不同浓度组在HIV-1病毒库数量、CD8^(+)T细胞亚群比例、CD8^(+)T细胞功能间的差异。结果与HCs(中位数416.71 ng/ml)相比HIV-1感染者(中位数539.16 ng/ml)血浆丙酮酸水平显著升高(P=0.0189)。与血浆低丙酮酸浓度组(低浓度组)相比,高丙酮酸浓度组(高浓度组)HIV-1细胞相关未剪接核糖核酸(HIV-1 cell associated un-spliced ribonucleic acid,HIV-1 CA RNA)、HIV-1 CA RNA/HIV-1 DNA的比值均显著升高;CD8^(+)T中央记忆T细胞(central memory T cells,TCM)比例显著升高;CD8^(+)T细胞表达TNF-α、IL-2、IFN-γ、CCL5的比例均降低,而表达CCL4的比例升高。血浆丙酮酸水平与CD8^(+)T细胞表达TNF-α(r=-0.3584,P=0.0106)、IL-2(r=-0.4975,P=0.0002)、IFN-γ(r=-0.4101,P=0.0031)、CCL5(r=-0.5655,P<0.0001)的比例呈负相关,与CCL4(r=0.4711,P=0.0014)的比例呈正相关。结论长期抗病毒治疗的HIV-1感染者血浆丙酮酸水平升高,且丙酮酸水平与HIV-1病毒库的活跃程度以及CD8^(+)T细胞功能紊乱相关。Objective To studyinvestigate the impact of plasma pyruvate on CD8^(+)T cell function and disease progression in people living with HIV-1.Methods A total of eleven healthy controls(HCs)and 55 HIV-1-infected patients receiving long-term antiretroviral therapy(ART)were enrolled.Plasma pyruvate levels in HIV-1-infected patients were measured by liquid chromatography-mass spectrometry to compare the differences in HIV-1 viral reservoir markers,CD8^(+)T cell subpopulation proportion and CD8^(+)T cell function between the different pyruvate concentration groups.Results Plasma pyruvate levels were significantly higher(P=0.0189)in people living with HIV-1(median 416.71 ng/ml)compared to HCs(median 539.16 ng/ml).The ratio of HIV-1 cell associated un-spliced ribonucleic acid(HIV-1 CA RNA)and HIV CA RNA/HIV DNA was significantly higher in the high plasma pyruvate concentration group than in the low concentration group.The proportion of central memory T cells(TCM)was significantly higher in the high concentration group.Furthermore The proportion of CD8^(+)T cells expressing TNF-α,IL-2,IFN-γand CCL5 was significantly lower and the proportion expressing CCL4 was significantly higher in the high concentration group.Plasma pyruvate levels were negatively correlated with the proportion of CD8^(+)T cells expressing TNF-α(r=-0.3584,P=0.0106),IL-2(r=-0.4975,P=0.0002),IFN-γ(r=-0.4101,P=0.0031)and CCL5(r=-0.5655,P<0.0001),and positively correlated with the proportion of CCL4(r=0.4711,P=0.0014).Conclusion HIV-1-infected patients receiving ART exhibited elevated plasma pyruvate levels,which are associated with the transcriptional activity of viral reservoir and the anti-HIV-1 function of CD8^(+)T cells.

关 键 词：Ⅰ型人类免疫缺陷病毒 病毒库 细胞免疫 CD8^(+)T细胞 能量代谢 丙酮酸 

分 类 号：R512.91[医药卫生—内科学]