Lymph Node Priming Licenses Intestinal CD103+ CD8 Tissue-Resident Memory T Cell Development

Abstract

Abstract CD8 tissue-resident memory T (TRM) cells provide front-line protective immunity at barrier tissues. Understanding TRM cell development will provide significant insights for vaccine design targeting infections and cancers at barrier tissues. Here, we demonstrate that pathogen-induced inflammation and pathogen-derived cognate antigen had minimal impact on intestinal CD103+ TRM cell differentiation. Instead, T cell priming in the mesenteric lymph nodes (MLN) was the principal determinant of CD103+ TRM cell differentiation in the intestine. In contrast, T cells primed in the spleen were incapable of differentiating into intestinal CD103+ TRM cells. Foodborne rechallenge of spleen-primed memory T cells was unable to induce intestinal CD103+ TRM cell differentiation, suggesting initial priming promoted a lasting fate. Moreover, both CD103− and CD103+ naïve T cells were highly efficient in differentiating into CD103+ TRM cells in the intestine after priming in the MLN, suggesting preconditioning of naïve T cells by TGF-b during homeostasis had little impact on intestinal CD103+ TRM cell differentiation. We further demonstrate that MLN priming initiated a CD103+ TRM cell program before effector T cell migration to the intestine and promoted CD103+ TRM cell differentiation in situ in part by promoting CCR9 expression and the ability to respond to TGF-b in a cell-extrinsic manner. Thus, mesenteric lymph node priming is specialized to license intestinal CD103+ CD8 TRM cell development.