T Cell Factor 1 Suppresses CD103+ Lung Tissue-Resident Memory T Cell Development

摘要

T cell factor 1 (Tcf1) promotes the central memory CD8sup+/sup T (TsubCM/sub) cell differentiation and stemness in lymphoid tissues after systemic infections. It remains unclear whether Tcf1 regulates the CD103suphigh/sup tissue-resident memory CD8sup+/sup T (TsubRM/sub) cell formation in non-lymphoid tissues after mucosal infections. We find that Tcf1 is progressively decreased during lung TsubRM/sub cell formation. Abrogation of transforming growth factor β (TGF-β) signaling is associated with a loss of CD103sup+/sup and reciprocal gain of Tcf1sup+/sup cells among TsubRM/sub precursors in?vivo . T-cell-specific ablation of Tcf7 enhances CD103 protein expression in TsubRM/sub cells and precursors and increases TsubRM/sub cell numbers after primary and secondary infections. Tcf1 directly binds to the Itgae (encoding CD103) locus and partly inhibits TGF-β-induced CD103 expression. Our study suggests that memory T?cell tissue residency and homeostatic proliferation are reciprocally regulated by Tcf1. Tcf1 may play either immunosupportive or immunosuppressive roles in CD8sup+/sup T?cells, depending on systemic or mucosal infections.