T细胞衰老与HIV-1感染者疾病进展及抗病毒治疗后免疫重建情况的相关性研究  

Investigation of the correlation between T cell senescence and disease progression as well as immune reconstitution post-antiretroviral therapy in HIV-1-infected individuals

作　　者：赵萌[1,2] 蒋梅青 张梦媛 杜娟 赵红心[3] 孔雅娴 ZHAO Meng;JIANG Meiqing;ZHANG Mengyuan;DU Juan;ZHAO Hongxin;KONG Yaxian(Peking University Ditan Teaching Hospital,Beijing 100015,China;Beijing Key Laboratory of Emerging Infectious Diseases,Institute of Infectious Diseases,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China;Clinical Center for AIDS,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China)

机构地区：[1]北京大学地坛医院教学医院,北京100015 [2]首都医科大学附属北京地坛医院传染病研究所,新发突发传染病研究北京市重点实验室,北京100015 [3]首都医科大学附属北京地坛医院艾滋病临床中心,北京100015

出　　处：《中国艾滋病性病》2025年第3期236-241,共6页Chinese Journal of Aids & STD

基　　金：国家自然科学基金面上项目(82171548);北京市高层次公共卫生技术人才建设项目(学科骨干-02-27);北京市医管中心项目(DFL20241802);北京市医院管理局临床医学发展专项(ZYLX202126)。

摘　　要：目的比较健康对照与不同疾病阶段的HIV-1感染者外周血中T细胞衰老水平,并系统探讨T细胞衰老水平与HIV-1疾病进展及抗病毒治疗后免疫重建情况的关系。方法入组符合标准的42例未经c ART的HIV-1感染者(TNs)、25例经c ART后的HIV-1感染者(cARTs)与20例年龄性别相匹配的健康对照(HCs),并将c ARTs分为免疫应答者(IRs)与免疫无应答者(INRs),通过多色流式细胞术检测细胞衰老指标,探究T细胞衰老水平与HIV-1疾病进展以及c ART后免疫重建情况的关系。结果与HCs相比,TNs的CD4及CD8细胞中SA-β-gal^(+)(CD4:8.2 vs.28.3,Z=4.512,P=0.0073;CD8:40.5 vs.76.5,Z=3.357,P=0.0024)、CD27^(-)CD28^(-)(CD4:2.12 vs.7.18,Z=3.424,P=0.0018;CD8:23.1 vs.38.8,Z=3.553,P=0.0011)与CD57^(+)(CD4:2.93 vs.5.97,Z=3.281,P=0.0031;CD8:21.5 vs.28.9,Z=3.993,P=0.0171)细胞比例均显著升高,且SA-β-gal^(+)和CD27-CD28-细胞比例与CD4细胞计数均呈显著负相关(CD4:r=-0.5778,-0.4734,均P<0.05;CD8:r=-0.7186,-0.4733,均P<0.05)。经c ART后,CD4细胞中SA-β-gal^(+)细胞比例较TNs降低(28.3 vs.12.1,Z=6.183,P=0.0002),并恢复至与HCs相近的水平(8.2 vs.12.1,Z=0.057,P=0.9991),与IRs相比,INRs的CD4细胞具有更高的SA-β-gal^(+)细胞比例(10.5 vs.14.8,t=2.744,P=0.0016),但CD8细胞的SA-β-gal^(+)细胞比例在TNs与c ARTs间未见存在显著差异(P>0.05)。CD4与CD8细胞中CD27-CD28-与CD57^(+)比例在TNs与cARTs中均未见存在显著差异(均P>0.05)。结论与HCs相比,HIV-1感染者T细胞衰老水平显著增加,并且TNs衰老水平与HIV-1疾病进展密切相关,c ART可部分恢复HIV-1感染导致的T细胞衰老,但仍然较HCs增高;与IRs相比,INRs的T细胞衰老程度显著增加。Objective This study aimed to compare the senescence levels of T cells in the peripheral blood ofhealthy controls and HIV-1 infected patients across different disease stages.Additionally,the relationship between T cell senescence and HIV-1 disease progression,as well as immune reconstitution following antiviral treatment,was systematically explored.Methods Overall,42 treatment-na?ve HIV-1 infected patients(TNs),25 HIV-1 infected individuals undergoing combination antiretroviral therapy(c ART),and 20 age-and sex-matched healthy controls(HCs)were recruited from Beijing Ditan Hospital.cARTs were further divided into immune responders(IRs)and nonresponders(INRs).Multiparameter flow cytometry was used to measure cellular senescence markers to investigate the relationship between T cell senescence and HIV-1 disease progression,as well as immune reconstitution following antiviral treatment.Results In comparison with HCs,the ratio of SA-β-gal^(gal+)(CD4:8.2 vs.28.3,Z=4.512,P=0.0073;CD8:40.5 vs.76.5,Z=3.357,P=0.0024),CD27^(+)-CD28^(+)-(CD4:2.12 vs.7.18,Z=3.424,P=0.0018;CD8:23.1 vs.38.8,Z=3.553,P=0.0011)and CD57^(+)+(CD4:2.93 vs.5.97,Z=3.281,P=0.0031;CD8:21.5 vs.28.9,Z=3.993,P=0.0171)cells were significantly elevated in both CD4 and CD8 cells of TNs.Additionally,the ratio of SA-β-gal^(+)+and CD27^(+)-CD28^(+)-cells exhibited significant negative correlations with CD4 cell counts(CD4:r=-0.5778,-0.4734,both P<0.05;CD8:r=-0.7186,-0.4733,both P<0.05).The ratio of SA-β-gal^(+)+cells of CD4cells was significantly reduced in cARTs compared to TNs(28.3 vs.12.1,Z=6.183,P=0.0002)and restored to levels similar to those of HCs(8.2 vs.12.1,Z=0.057,P=0.9991).Furthermore,INRs had higher ratio of SA-β-gal^(+)+CD4 cells compared to IRs(10.5 vs.14.8,t=2.744,P=0.0016).However,no significant difference was found in SA-β-gal activity of CD8 cells between TNs and cARTs(P>0.05).Additionally,the ratios of CD27^(+)-CD28^(+)-and CD57^(+)+cells in both CD4+and CD8+cells were not significantly different between TNs and cARTs(all P>0.05).Conclusi

关 键 词：1型艾滋病病毒 T细胞 免疫衰老 抗反转录病毒治疗 

分 类 号：R512.91[医药卫生—内科学] R373.9[医药卫生—临床医学]