MAdCAM-1 co-stimulation combined with retinoic acid and TGF-β induces blood CD8 T cells to adopt a gut CD101 T phenotype.

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.

MAdCAM-1 costimulation in the presence of retinoic acid and TGF-β promotes HIV infection and differentiation of CD4+ T cells into CCR5+ TRM-like cells.

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.