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研究感染 HIV-1 的印度患者中 CD4+CD8+ 双阳性 T 淋巴细胞表型和功能。

Study of CD4+CD8+ double positive T-lymphocyte phenotype and function in Indian patients infected with HIV-1.

机构信息

Department of Microbiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

出版信息

J Med Virol. 2012 Jun;84(6):845-56. doi: 10.1002/jmv.23289.

DOI:10.1002/jmv.23289
PMID:22499005
Abstract

CD4+CD8+ double positive T cells represent a minor peripheral blood lymphocyte population. CD4+ expression on CD8+ T cells is induced following cellular activation, and as chronic HIV-1 infection is associated with generalized immune activation, double positive T cells studies have become necessary to understand the immunopathology of human immunodeficiency virus (HIV). The frequency of double positive T cells in persons infected with HIV was studied in comparison to uninfected controls. Further, the expression of CD38, HLA-DR, and programmed death (PD)-1 on these cells were ascertained. HIV-1 specific double positive T cells were also studied for their cytokine secretory ability and phenotype. A significantly higher double positive cell population was observed in the patients with advanced HIV disease (CD4+ T cell counts below 200 cells/µl), as compared to patients with CD4+ T cell counts above 500 cells/µl. Double positive T cells from patients with symptomatic HIV disease had a significantly increased activation and exhaustion levels, compared to asymptomatic subjects and to single positive T cells from the same subjects. HIV-1 specific double positive T cells showed further increase in CD38 and PD-1 expression levels. The proportion of CD38 and PD-1 expressing total and HIV-1 specific double positive T cells correlated positively with HIV-1 plasma viremia and negatively with CD4+ T cell counts. HIV infection results in a marked increase of double positive T cell population, and this cell population shows higher level of activation and exhaustion (increased PD-1 expression) compared to the single positive CD4+ and CD8+ T cells.

摘要

CD4+CD8+ 双阳性 T 细胞代表外周血淋巴细胞的一个小群体。CD8+T 细胞上的 CD4+表达是在细胞活化后诱导的,由于慢性 HIV-1 感染与全身免疫激活有关,因此研究双阳性 T 细胞对于理解人类免疫缺陷病毒 (HIV) 的免疫病理学变得非常必要。本研究比较了 HIV 感染者和未感染者外周血中双阳性 T 细胞的频率,并进一步确定了这些细胞上 CD38、HLA-DR 和程序性死亡 (PD)-1 的表达。还研究了 HIV-1 特异性双阳性 T 细胞的细胞因子分泌能力和表型。与 CD4+T 细胞计数大于 500 个/µl 的患者相比,CD4+T 细胞计数低于 200 个/µl 的晚期 HIV 疾病患者中观察到双阳性细胞群体显著增加。与无症状受试者和来自同一受试者的单阳性 T 细胞相比,患有有症状 HIV 疾病的双阳性 T 细胞具有明显增加的激活和耗竭水平。HIV-1 特异性双阳性 T 细胞的 CD38 和 PD-1 表达水平进一步增加。CD38 和 PD-1 表达的总双阳性和 HIV-1 特异性双阳性 T 细胞的比例与 HIV-1 血浆病毒载量呈正相关,与 CD4+T 细胞计数呈负相关。HIV 感染导致双阳性 T 细胞群体显著增加,与单阳性 CD4+和 CD8+T 细胞相比,该细胞群体显示出更高水平的激活和耗竭(PD-1 表达增加)。

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