Tissue-Specific Cues Direct Fate Decisions of Mucosal Memory T Cells (39.21)

Abstract

Abstract Mucosal memory CD8 T cells are characterized by their location at peripheral interfaces and the ability to immediately exhibit effector functions. By contrast, lymphoid memory T cells reside within lymphoid tissues and require further differentiation to become effectors. Both memory subtypes contribute to protective immunity, but the accumulation of mucosal effector memory T cells at pathogen portals forms a central component of protective immunity. The process that drives the compartmentalization and functional differentiation of this memory subset is poorly understood. Here we show that the thymus leukemia (TL) antigen, a ligand for the TCR co-repressor, CD8αα, serves a key role in the molecular mechanism that determines the fate of mucosal CD8αβ+ effector T cells. TL specifically controls the survival of CD8αα+CD8αβ+ effectors, but eliminates CD8αα negative CD8αβ effectors. This TL-CD8αα-mediated process allows the intestinal environment to selectively preserve the "fittest" effector cells to become mucosal memory T cells that form the first line of immune protection.