[Study on the correlation between viral load and activation and exhaustion levels of CD8+T cells in HIV/AIDS patients]

Zhonghua Yu Fang Yi Xue Za Zhi. 2024 Nov 6;58(11):1690-1696. doi: 10.3760/cma.j.cn112150-20231219-00462.
[Article in Chinese]

Abstract

Objective: To 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). Methods: A 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. Results: Among the 81 HIV/AIDS patients, 69 (85.19%) were males and 12 (14.81%) were females, with an age M (Q1, Q3) 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≤105 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>105 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). Conclusions: The 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.

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MQ1Q3)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≤105 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>105 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。.

Publication types

  • English Abstract

MeSH terms

  • ADP-ribosyl Cyclase 1* / metabolism
  • Acquired Immunodeficiency Syndrome* / immunology
  • Adult
  • CD8-Positive T-Lymphocytes* / immunology
  • Case-Control Studies
  • Female
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1
  • HLA-DR Antigens* / metabolism
  • Humans
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor* / metabolism
  • RNA, Viral
  • Viral Load*
  • Young Adult

Substances

  • Programmed Cell Death 1 Receptor
  • ADP-ribosyl Cyclase 1
  • HLA-DR Antigens
  • PDCD1 protein, human
  • RNA, Viral