CXCR6 promotes dermal CD8+ T cell survival and transition to long-term tissue residence.

ABSTRACT

Tissue resident memory T cells (TRM) provide important protection against infection, and yet the interstitial signals necessary for their formation and persistence remain incompletely understood. Here we show that antigen-dependent induction of the chemokine receptor, CXCR6, is a conserved requirement for TRM formation in peripheral tissue after viral infection. CXCR6 was dispensable for the early accumulation of antigen-specific CD8+ T cells in skin and did not restrain their exit. Single cell sequencing indicated that CXCR6-/- CD8+ T cells were also competent to acquire a transcriptional program of residence but exhibited deficiency in multiple pathways that converged on survival and metabolic signals necessary for memory. As such, CXCR6-/- CD8+ T cells exhibited increased rates of apoptosis relative to controls in the dermis, leading to inefficient TRM formation. CXCR6 expression may therefore represent a common mechanism across peripheral non-lymphoid tissues and inflammatory states that increases the probability of long-term residence.