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

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.