Department of Molecular Immunology and Microbiology, Indian Council of Medical Research-National Institute for Research in Reproductive Health, Mumbai, India.
Department of Biochemistry and Virology, Indian Council of Medical Research-National Institute for Research in Reproductive Health, Mumbai, India.
Front Immunol. 2021 Mar 22;12:651122. doi: 10.3389/fimmu.2021.651122. eCollection 2021.
Integrin αβ expressing CD4 T cells are preferred targets for HIV infection and are thought to be predictors of disease progression. Concurrent analysis of integrin αβ expressing innate and adaptive immune cells was carried out in antiretroviral (ART) therapy naïve HIV infected women in order to determine its contribution to HIV induced immune dysfunction. Our results demonstrate a HIV infection associated decrease in the frequency of integrin αβ expressing endocervical T cells along with an increase in the frequency of integrin αβ expressing peripheral monocytes and central memory CD4 T cells, which are considered to be viral reservoirs. We report for the first time an increase in levels of soluble MAdCAM-1 (sMAdCAM-1) in HIV infected individuals as well as an increased frequency and count of integrin CD8 memory T cells. Correlation analysis indicates that the frequency of effector memory CD8 T cells expressing integrin αβ is associated with levels of both sMAdCAM-1 and TGF-β1. The results of this study also suggest HIV induced alterations in T cell homeostasis to be on account of disparate actions of sMAdCAM-1 and TGF-β1 on integrin αβ expressing T cells. The immune correlates identified in this study warrant further investigation to determine their utility in monitoring disease progression.
整合素 αβ 表达的 CD4 T 细胞是 HIV 感染的首选靶细胞,被认为是疾病进展的预测因子。为了确定其对 HIV 诱导的免疫功能障碍的贡献,我们对接受抗逆转录病毒 (ART) 治疗前的 HIV 感染女性中的整合素 αβ 表达先天和适应性免疫细胞进行了同时分析。我们的研究结果表明,HIV 感染与宫颈内 T 细胞中整合素 αβ 表达的频率降低有关,同时外周单核细胞和中央记忆 CD4 T 细胞中整合素 αβ 表达的频率增加,这些细胞被认为是病毒储存库。我们首次报道了 HIV 感染个体中可溶性 MAdCAM-1(sMAdCAM-1)水平的增加,以及整合素 CD8 记忆 T 细胞的频率和计数的增加。相关性分析表明,表达整合素 αβ 的效应记忆 CD8 T 细胞的频率与 sMAdCAM-1 和 TGF-β1 的水平相关。本研究的结果还表明,HIV 诱导的 T 细胞动态平衡改变是由于 sMAdCAM-1 和 TGF-β1 对整合素 αβ 表达 T 细胞的不同作用所致。本研究中确定的免疫相关性值得进一步研究,以确定它们在监测疾病进展中的应用。