Targeted Expansion of Tissue-Resident CD8+ T Cells to Boost Cellular Immunity in the Skin

SUMMARY Tissue-resident memory (T RM ) CD8 + T cells are positioned within environmental barrier tissues to provide a first line of defense against pathogen entry, but whether these specialized T cell populations can be readily boosted to increase protective immunity is ill defined. Here, we demonstrate that repeated activation of rare, endogenous T RM CD8 + T cells, using only topical application of antigenic peptide causes delayed-type hypersensitivity and increases the number of antigen-specific T RM CD8 + T cells, specifically in the challenged skin by ~15-fold. Expanded T rm CD8 + T cells in the skin are derived from memory T cells recruited out of the circulation that became CD69 + tissue residents following a local antigen encounter. Notably, recruited circulating memory CD8 + T cells of a different antigen specificity could be coerced to become tissue resident using a dual-peptide challenge strategy. Expanded T RM CD8 + T cells significantly increase anti-viral protection, suggesting that this approach could be used to rapidly boost tissue-specific cellular immunity.