Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Curr Opin HIV AIDS. 2019 Mar;14(2):115-120. doi: 10.1097/COH.0000000000000529.
Trafficking of lymphocytes into and between gut inductive and effector sites of the gut tissues is regulated by integrin α4β7. Recent findings that describe the central role of α4β7 CD4 T cells in HIV pathogenesis, and the possibility of targeting these cells to prevent or treat HIV infection will be reviewed.
Recent reports indicate that the frequency of α4β7 CD4 T cells is directly correlated with the risk of HIV acquisition and CD4 T-cell decline post infection. MAdCAM -mediated signaling through α4β7, in the presence of retinoic acid, supports viral replication in recently activated naïve CD4 T cells. Treatment of HIV-infected patients with vedolizumab, an α4β7 antagonist, is well tolerated, and reduces the size and number of lymphoid aggregates in gut associated lymphoid tissues.
Integrin α4β7 underlies one of the principal mechanisms that CD4 T cells employ to traffic to the gut. It also defines a subset of cells that play a significant role in HIV transmission and pathogenesis. Understanding how α4β7 facilitates gut homing may provide insight into key aspects of HIV transmission, pathogenesis, and the formation of viral reservoirs. Targeting α4β7 may have utility in the prevention and treatment of HIV infection.
综述目的：淋巴细胞在肠道组织的诱导和效应部位之间的迁移受到整合素 α4β7 的调节。本文将综述描述 α4β7 CD4 T 细胞在 HIV 发病机制中的核心作用，以及靶向这些细胞以预防或治疗 HIV 感染的可能性。
最新发现：最近的报告表明，α4β7 CD4 T 细胞的频率与 HIV 感染的风险以及感染后 CD4 T 细胞的下降直接相关。在维得利珠单抗（一种 α4β7 拮抗剂）治疗下，MAdCAM 通过 α4β7 介导的信号转导，在维甲酸存在的情况下，支持新激活的幼稚 CD4 T 细胞中的病毒复制。α4β7 拮抗剂维得利珠单抗治疗 HIV 感染患者耐受性良好，可减少肠道相关淋巴组织中淋巴聚集的大小和数量。
总结：整合素 α4β7 是 CD4 T 细胞迁移到肠道的主要机制之一。它还定义了在 HIV 传播和发病机制中起重要作用的细胞亚群。了解 α4β7 如何促进肠道归巢可能为 HIV 传播、发病机制和病毒库的形成提供关键方面的见解。靶向 α4β7 可能对 HIV 感染的预防和治疗具有实用价值。
