Retinoic acid signaling during priming licenses intestinal CD103(+) CD8 T(RM) cell differentiation

CD8 tissue-resident memory T (T(RM)) cells provide frontline protection at barrier tissues; however, mechanisms regulating T(RM) cell development are not completely understood. Priming dictates the migration of effector T cells to the tissue, while factors in the tissue induce in situ T(RM) cell differentiation. Whether priming also regulates in situ T(RM) cell differentiation uncoupled from migration is unclear. Here, we demonstrate that T cell priming in the mesenteric lymph nodes (MLN) regulates CD103(+) T(RM) cell differentiation in the intestine. In contrast, T cells primed in the spleen were impaired in the ability to differentiate into CD103(+) T(RM) cells after entry into the intestine. MLN priming initiated a CD103(+) T(RM) cell gene signature and licensed rapid CD103(+) T(RM) cell differentiation in response to factors in the intestine. Licensing was regulated by retinoic acid signaling and primarily driven by factors other than CCR9 expression and CCR9-mediated gut homing. Thus, the MLN is specialized to promote intestinal CD103(+) CD8 T(RM) cell development by licensing in situ differentiation.