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

Abstract

Summary: T cell factor 1 (Tcf1) promotes the central memory CD8+ T (TCM) cell differentiation and stemness in lymphoid tissues after systemic infections. It remains unclear whether Tcf1 regulates the CD103high tissue-resident memory CD8+ T (TRM) cell formation in non-lymphoid tissues after mucosal infections. We find that Tcf1 is progressively decreased during lung TRM cell formation. Abrogation of transforming growth factor β (TGF-β) signaling is associated with a loss of CD103+ and reciprocal gain of Tcf1+ cells among TRM precursors in vivo. T-cell-specific ablation of Tcf7 enhances CD103 protein expression in TRM cells and precursors and increases TRM 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 CD8+ T cells, depending on systemic or mucosal infections. : Tcf1 promotes circulating memory T cell development and maintenance after systemic infections. Wu et al. show that Tcf1 inhibits CD103+ resident memory T cell development in influenza-virus-infected mice. Tcf1 may either promote or suppress memory T cell development, depending on systemic or mucosal infections. Keywords: TRM, influenza, memory CD8+ T cells, Tcf1, CD103