论著
ENGLISH ABSTRACT
HIV/AIDS患者病毒载量与CD8 +T细胞活化及耗竭水平的相关性研究
詹洁琼
宋黎黎
林怡
董原
王宇
褚维
作者及单位信息
·
DOI: 10.3760/cma.j.cn112150-20231219-00462
Study on the correlation between viral load and activation and exhaustion levels of CD8 +T cells in HIV/AIDS patients
Zhan Jieqiong
Song Lili
Lin Yi
Dong Yuan
Wang Yu
Chu Wei
Authors Info & Affiliations
Zhan Jieqiong
Department of Microbiological Laboratory, Centers for Disease Control and Prevention of Huangpu District, Shanghai200023, China
Song Lili
Centers for Disease Control and Prevention of Huangpu District, Shanghai200023, China
Lin Yi
Division of Tuberculosis and HIV/AIDS Control and Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai200336, China
Dong Yuan
Division of Tuberculosis and HIV/AIDS Control and Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai200336, China
Wang Yu
Department of Microbiological Laboratory, Centers for Disease Control and Prevention of Huangpu District, Shanghai200023, China
Chu Wei
Department of Microbiological Laboratory, Centers for Disease Control and Prevention of Huangpu District, Shanghai200023, China
·
DOI: 10.3760/cma.j.cn112150-20231219-00462
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摘要

目的探讨并分析人类免疫缺陷病毒(HIV)/获得性免疫缺陷综合征(AIDS)患者外周血CD8 +T细胞上CD38、HLA-DR和程序性死亡蛋白-1(PD-1)的表达水平与HIV-1 RNA病毒载量、免疫活化和耗竭的相关性。

方法纳入HIV/AIDS患者81例(未接受抗病毒治疗者64例,接受治疗者17例)、同期40例健康捐献者作为对照组。采用流式细胞术分析CD4 +T淋巴细胞计数和CD8 +T细胞上活化标志物CD38、HLA-DR和凋亡标志物PD-1的表达水平,通过实时荧光定量聚合酶链反应定量检测HIV-1感染者血浆中的 HIV-1 RNA。采用方差分析比较HIV/AIDS患者与健康对照组CD8 +T细胞CD38、HLA-DR、PD-1的表达水平;采用Spearman相关性分析不同T淋巴细胞计数与HIV RNA病毒载量的相关性以及病毒载量与外周血CD8 +T细胞CD38、HLA-DR和PD-1的相关性。

结果81例HIV/AIDS患者中,男性69例(85.19%),女性12例(14.81%),年龄 MQ 1Q 3)为58(36.5,65.0)岁;年龄超过55岁以上的HIV/AIDS患者60例(74.07%),18~55岁HIV/AIDS患者21例(25.93%)。方差分析结果显示,与健康人群对照组相比,HIV/AIDS患者CD38、HLA-DR、PD-1在CD8 +T细胞上表达水平增加(均 P<0.05),并且在CD4 +T细胞计数小于350 cells/μl的患者中,CD38、HLA-DR与PD-1的表达增加更高(均 P<0.05)。Spearman相关性分析结果显示,HIV/AIDS患者CD4 +、CD4+/CD8 +与病毒载量呈负相关( r分别为-0.407、-0.378,均 P<0.05),CD8 +与病毒载量呈正相关( r=0.356, P<0.05);当HIV RNA水平≤10 5 CPs/ml时,HIV RNA水平与CD8 +T细胞CD38、HLA-DR、PD-1的表达水平无相关性(均 P>0.05),当HIV RNA水平>10 5 CPs/ml时,HIV RNA水平与CD8 +T细胞CD38、HLA-DR、PD-1的表达水平呈正相关( r分别为0.412、0.387、0.395,均 P<0.05)。

结论HIV/AIDS患者外周血CD8 +T细胞上CD38、HLA-DR活化水平升高、PD-1表达上调;当病毒载量较高时,患者HIV RNA病毒载量与CD8 +T细胞活化和耗竭水平呈正相关。

HIV RNA;CD8 +T细胞 ;细胞活化;细胞凋亡
ABSTRACT

ObjectiveTo investigate and analyze the correlation between the expression levels of CD38, HLA-DR and programmed cell death-1 (PD-1) on peripheral blood CD8 +T cells and HIV-1 RNA viral load, immune activation and exhaustion in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS).

MethodsA total of 81 HIV/AIDS patients (64 without antiretroviral therapy and 17 with therapy) and 40 healthy donors in the same period were enrolled as the control group. Flow cytometry was used to analyze the CD4 +T lymphocyte count and the expression levels of activation markers CD38 and HLA-DR and apoptosis marker PD-1 on CD8 +T cells. HIV-1 RNA in the plasma of HIV-1 infected patients was quantitatively detected by real-time fluorescence quantitative polymerase chain reaction. Variance analysis was used to compare the expression levels of CD38, HLA-DR and PD-1 on CD8 +T cells between HIV/AIDS patients and healthy controls. Spearman correlation analysis was used to analyze the correlation between different T lymphocyte counts and HIV RNA viral load, and the correlation between HIV RNA viral load and peripheral blood CD8 +T cell CD38, HLA-DR and PD-1.

ResultsAmong the 81 HIV/AIDS patients, 69 (85.19%) were males and 12 (14.81%) were females, with an age M ( Q 1 , Q 3) of 58 (36.5, 65.0) years. There were 60 HIV/AIDS patients over 55 years old (74.07%) and 21 HIV/AIDS patients between 18 and 55 years old (25.93%). The results of variance analysis showed that compared with the healthy control group, the expression levels of CD38, HLA-DR and PD-1 on CD8 +T cells in HIV/AIDS patients increased, and the differences were statistically significant (all P<0.05). In addition, the expression of CD38, HLA-DR and PD-1 increased significantly in patients with CD4 +T cell count less than 350 cells/μl, and the differences were statistically significant (all P<0.05). Spearman correlation analysis showed that CD4 +and CD4 +/CD8 +were negatively correlated with viral load in HIV/AIDS patients ( r=-0.407 and -0.378, respectively, both P<0.05), and CD8 +was positively correlated with viral load ( r=0.356, P<0.05). When the HIV RNA level was≤10 5 CPs/ml, there was no correlation between the HIV RNA level and the expression levels of CD38, HLA-DR and PD-1 on CD8 +T cells (all P>0.05). However, when the level of HIV RNA was>10 5 CPs/ml, the level of HIV RNA was positively correlated with the expression levels of CD38, HLA-DR and PD-1 on CD8 +T cells ( r=0.412, 0.387, 0.395, respectively, all P<0.05).

ConclusionsThe activation levels of CD38 and HLA-DR and the expression of PD-1 on CD8 +T cells in the peripheral blood of HIV/AIDS patients are increased. When the viral load is high, the HIV RNA viral load is positively correlated with the activation and exhaustion levels of CD8 +T cells.

HIV RNA;CD8 +T cells ;Cell activation;Cell apoptosis
Song Lili, Email: mocdef.3ab6193617810531
引用本文

詹洁琼,宋黎黎,林怡,等. HIV/AIDS患者病毒载量与CD8 +T细胞活化及耗竭水平的相关性研究 [J]. 中华预防医学杂志,2024,58(11):1690-1696.

DOI:10.3760/cma.j.cn112150-20231219-00462

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艾滋病(AIDS)是一种高病死率的慢性传染病,主要通过人类免疫缺陷病毒(HIV)感染而引起。感染HIV病毒后,随着时间推移,免疫系统逐渐受损,导致机体对各种常见微生物包括细菌、病毒、真菌和寄生虫等以及肿瘤的发展失去抵抗能力,因此T细胞的免疫功能在艾滋病的疾病进展中起着至关重要的作用,而其最主要的特征之一就是CD4 +T淋巴细胞减少,免疫功能减退 1,CD8 +T淋巴细胞数量增多,CD4 +/CD8 +比例失调 2。有研究发现,人类机体感染HIV病毒后的细胞免疫活化程度与CD8 +T细胞上的CD38、HLA-DR 3的表达水平相关联,这为增强HIV/AIDS患者的免疫功能和提高抗病毒治疗效果提供了新的思路。免疫活化与耗竭对于CD8 +T细胞效应功能的影响具有双重性 4,免疫活化可以促使CD8 +T细胞增殖和分化,提高其杀伤能力和产生多种效应分子的能力 5。活化状态下的CD8 +T细胞可以迅速识别并消灭感染体内的病原微生物或异常细胞,起到保护机体健康的作用 6 , 7。随着T细胞的活化,功能衰竭和凋亡相关的协同刺激分子程序性死亡蛋白-1(Programmed Cell Death 1,PD-1)被诱导表达于CD4 +T细胞和CD8 +T细胞的表面 8 , 9,以抑制过度活化的效应T细胞。因此,通过对CD8 +T细胞上CD38、HLA-DR和PD-1的表达情况进行评估,可从免疫活化与耗竭角度研究HIV-1感染过程中CD8 +T细胞的动态变化及其功能。
近年来,T细胞的衰减机制和衰减状态的恢复已经成为HIV免疫治疗领域的关注焦点,目前病毒学指标(以病毒载量为主)常用于评估HIV/AIDS患者免疫状况及抗病毒治疗效果,也是预测疾病进展速度的重要指标,无论是单独评估还是与CD4 +T细胞计数相结合,均具有很高的预后意义。淋巴细胞计数和病毒载量水平在一定程度上亦可作为机体免疫活化程度的指标。因此,本研究从病毒学和免疫学的角度深入探讨HIV/AIDS患者的免疫状态水平,分析CD8 +T细胞在HIV感染过程中的活化和耗竭水平的变化特征,利用免疫抑制和免疫促进双向调节的优势,以期为寻找新的治疗靶点以逆转免疫抑制并增强抗病毒免疫应答,进而发挥抗HIV的作用来提高患者生活质量。
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备注信息
A
宋黎黎,Email: mocdef.3ab6193617810531
B
复旦大学公共卫生学院流行病学教研室院长助理丁盈盈副教授和上海市黄浦区疾病预防控制中心结核病与艾滋病防治科吴健副主任医师的帮助和指导
C
詹洁琼, 宋黎黎, 林怡, 等. HIV/AIDS患者病毒载量与CD8 +T细胞活化及耗竭水平的相关性研究[J]. 中华预防医学杂志, 2024, 58(11): 1690-1696. DOI: 10.3760/cma.j.cn112150-20231219-00462.
D
所有作者声明无利益冲突
E
上海市疾病预防控制青年骨干人才培养项目 (22QNGG24)
2023年度上海市黄浦区卫生健康委员会科研项目 (HLM202329)
2023年度黄浦区医学培育专科建设黄浦区公共卫生应急响应(重点)实验室 (2023PYZK04)
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