Paiardini Mirko, Cervasi Barbara, Albrecht Helmut, Muthukumar Alagarraju, Dunham Richard, Gordon Shari, Radziewicz Henry, Piedimonte Giuseppe, Magnani Mauro, Montroni Maria, Kaech Susan M, Weintrob Amy, Altman John D, Sodora Donald L, Feinberg Mark B, Silvestri Guido
Department of Medicine, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
J Immunol. 2005 Mar 1;174(5):2900-9. doi: 10.4049/jimmunol.174.5.2900.
The immunodeficiency that follows HIV infection is related to the virus-mediated killing of infected CD4(+) T cells, the chronic activation of the immune system, and the impairment of T cell production. In this study we show that in HIV-infected individuals the loss of IL-7R (CD127) expression defines the expansion of a subset of CD8(+) T cells, specific for HIV as well as other Ags, that show phenotypic (i.e., loss of CCR7 and CD62 ligand expression with enrichment in activated and/or proliferating cells) as well as functional (i.e., production of IFN-gamma, but not IL-2, decreased ex vivo proliferative potential and increased susceptibility to apoptosis) features of effector T cells. Importantly, in HIV-infected individuals the levels of CD8(+)CD127(-) T cells are directly correlated with the main markers of disease progression (i.e., plasma viremia and CD4(+) T cell depletion) as well as with the indices of overall T cell activation. In all, these results identify the expansion of CD8(+)CD127(-) effector-like T cells as a novel feature of the HIV-associated immune perturbation. Further studies are thus warranted to determine whether measurements of CD127 expression on CD8(+) T cells may be useful in the clinical management of HIV-infected individuals.
HIV感染后出现的免疫缺陷与病毒介导的感染CD4(+) T细胞的杀伤、免疫系统的慢性激活以及T细胞生成受损有关。在本研究中，我们发现，在HIV感染个体中，IL-7R（CD127）表达缺失定义了一类CD8(+) T细胞亚群的扩增，这类细胞对HIV以及其他抗原具有特异性，表现出效应T细胞的表型特征（即CCR7和CD62配体表达缺失，在活化和/或增殖细胞中富集）以及功能特征（即产生IFN-γ，但不产生IL-2，体外增殖潜能降低，对凋亡的敏感性增加）。重要的是，在HIV感染个体中，CD8(+)CD127(-) T细胞水平与疾病进展的主要标志物（即血浆病毒血症和CD4(+) T细胞耗竭）以及总体T细胞激活指数直接相关。总之，这些结果确定CD8(+)CD127(-) 效应样T细胞的扩增是HIV相关免疫紊乱的一个新特征。因此，有必要进一步研究以确定检测CD8(+) T细胞上CD127的表达是否有助于HIV感染个体的临床管理。
