Girard Alexandre, Vimonpatranon Sinmanus, Chan Amanda, Jiang Andrew, Huang Da Wei, Virtaneva Kimmo, Kanakabandi Kishore, Martens Craig, Goes Livia R, Soares Marcelo A, Licavoli Isabella, McMurry Jordan, Doan Pearl, Wertz Samuel, Wei Danlan, Ryk Donald Van, Ganesan Sundar, Hwang Il Young, Kehrl John H, Martinelli Elena, Arthos James, Cicala Claudia
National Institute of Allergy and Infectious Diseases, Laboratory of Immunoregulation, Bethesda, Maryland, USA.
National Institute of Allergy and Infectious Diseases, Laboratory of Immunoregulation, Bethesda, Maryland, USA; Department of Retrovirology, Walter Reed Army Institute of Research-Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Mucosal Immunol. 2024 Aug;17(4):700-712. doi: 10.1016/j.mucimm.2024.04.004. Epub 2024 May 8.
Resident memory T cells (Ts) help control local immune homeostasis and contribute to tissue-protective immune responses. The local cues that guide their differentiation and localization are poorly defined. We demonstrate that mucosal vascular addressin cell adhesion molecule 1, a ligand for the gut-homing receptor αβ integrin, in the presence of retinoic acid and transforming growth factor-β (TGF-β) provides a co-stimulatory signal that induces blood cluster of differentiation (CD8 T cells to adopt a T-like phenotype. These cells express CD103 (integrin α) and CD69, the two major T cell-surface markers, along with CD101. They also express C-C motif chemokine receptors 5 (CCR5) , C-C motif chemokine receptors 9 (CCR9), and αβ, three receptors associated with gut homing. A subset also expresses E-cadherin, a ligand for αβ. Fluorescent lifetime imaging indicated an αβ and E-cadherin cis interaction on the plasma membrane. This report advances our understanding of the signals that drive the differentiation of CD8 T cells into resident memory T cells and provides a means to expand these cells in vitro, thereby affording an avenue to generate more effective tissue-specific immunotherapies.
驻留记忆性T细胞（Ts）有助于控制局部免疫稳态，并参与组织保护性免疫反应。然而，引导其分化和定位的局部信号尚不清楚。我们证明，在视黄酸和转化生长因子-β（TGF-β）存在的情况下，肠道归巢受体αβ整合素的配体——黏膜血管地址素细胞黏附分子1，提供了一个共刺激信号，诱导血液中分化簇（CD8）T细胞采用类似Ts的表型。这些细胞表达两种主要的T细胞表面标志物CD103（整合素αE）和CD69，以及CD101。它们还表达C-C基序趋化因子受体5（CCR5）、C-C基序趋化因子受体9（CCR9）和α4β7，这三种与肠道归巢相关的受体。其中一个亚群还表达αE-钙黏蛋白，它是α4β7的配体。荧光寿命成像表明，在质膜上存在α4β7和αE-钙黏蛋白的顺式相互作用。本报告增进了我们对驱动CD8 T细胞分化为驻留记忆性T细胞的信号的理解，并提供了一种在体外扩增这些细胞的方法，从而为产生更有效的组织特异性免疫疗法提供了一条途径。
