Transforming Growth Factor-β Signaling Controls the Formation and Maintenance of Gut-Resident Memory T Cells by Regulating Migration and Retention

Tissue-resident memory T (Trm) cells represent a population of memory CD8(+) T cells that can act as first responders to local infection. The mechanisms regulating the formation and maintenance of intestinal Trm cells remain elusive. Here we showed that transforming growth factor-beta (TGF-beta) controlled both stages of gut Trm cell differentiation through different mechanisms. During the formation phase of Trm cells, TGF-beta signaling inhibited the migration of effector CD8(+) T cells from the spleen to the gut by dampening the expression of integrin alpha 4 beta 7. During the maintenance phase, TGF-beta was required for the retention of intestinal Trm cells at least in part through the induction of integrins alpha E beta 7 and alpha 1, as well as CD69. Thus, the cytokine acts to control cytotoxic T cell differentiation in lymphoid and peripheral organs.