CXCR6 Promotes Dermal CD8⁺ T Cell Survival and Transition to Long-Term Tissue Residence

Resident memory T cells (T_RM) provide localized protection due to their position in barrier tissues. However, interstitial signals necessary for their formation and persistence are not properly understood. This study demonstrated that antigen-dependent induction of the chemokine receptor, CXCR6, is a conserved requirement for T_RM formation in peripheral tissue after viral infection. Cutaneous murine viral infection was used to define the kinetics of CXCR6 expression and its impact on the transition of effector CD8⁺ T cells to long-term tissue residence. To understand where CXCR6 is turned on in the T_RM differentiation trajectory, single-cell RNA sequencing was performed on interstitial CD8⁺ T cells. Congenically distinct, OT-1 T cells were transferred intravenously into C57BL/6J mice. The following day, mice were infected with vaccinia virus expressing OVA_257–264. Live, extravascular OT-1 T cells were sorted from infected skin 21 days post infection and submitted for single-cell RNA sequencing to capture cells at the beginning of memory formation.