Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America.
Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
PLoS Pathog. 2023 Mar 10;19(3):e1011209. doi: 10.1371/journal.ppat.1011209. eCollection 2023 Mar.
CD4+ tissue resident memory T cells (TRMs) are implicated in the formation of persistent HIV reservoirs that are established during the very early stages of infection. The tissue-specific factors that direct T cells to establish tissue residency are not well defined, nor are the factors that establish viral latency. We report that costimulation via MAdCAM-1 and retinoic acid (RA), two constituents of gut tissues, together with TGF-β, promote the differentiation of CD4+ T cells into a distinct subset α4β7+CD69+CD103+ TRM-like cells. Among the costimulatory ligands we evaluated, MAdCAM-1 was unique in its capacity to upregulate both CCR5 and CCR9. MAdCAM-1 costimulation rendered cells susceptible to HIV infection. Differentiation of TRM-like cells was reduced by MAdCAM-1 antagonists developed to treat inflammatory bowel diseases. These finding provide a framework to better understand the contribution of CD4+ TRMs to persistent viral reservoirs and HIV pathogenesis.
CD4+组织驻留记忆 T 细胞（TRM）参与了在感染早期形成的持续性 HIV 储存库的形成。指导 T 细胞建立组织驻留的组织特异性因素尚未得到很好的定义，也没有确定建立病毒潜伏期的因素。我们报告说，肠道组织的两个组成部分——MAdCAM-1 和视黄酸（RA）以及 TGF-β 通过共刺激作用，促进 CD4+T 细胞分化为一个独特的 α4β7+CD69+CD103+TRM 样细胞亚群。在我们评估的共刺激配体中，MAdCAM-1 是唯一能够上调 CCR5 和 CCR9 的配体。MAdCAM-1 的共刺激作用使细胞容易感染 HIV。用于治疗炎症性肠病的 MAdCAM-1 拮抗剂可减少 TRM 样细胞的分化。这些发现为更好地理解 CD4+TRM 对持续性病毒储存库和 HIV 发病机制的贡献提供了框架。
