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

摘要

Tissue-resident memory (TsubRM/sub) CD8sup+/sup 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 TsubRM/sub CD8sup+/sup T?cells, using only topical application of antigenic peptide causes delayed-type hypersensitivity and increases the number of antigen-specific TsubRM/sub CD8sup+/sup T?cells, specifically in the challenged skin by ～15-fold. Expanded TsubRM/sub CD8sup+/sup T?cells in the skin are derived from memory T?cells recruited out of the circulation that became CD69sup+/sup tissue residents following a local antigen encounter. Notably, recruited circulating memory CD8sup+/sup T?cells of a different antigen specificity could be coerced to become tissue resident using a dual-peptide challenge strategy. Expanded TsubRM/sub CD8sup+/sup T?cells significantly increase anti-viral protection, suggesting that this approach could be used to rapidly boost tissue-specific cellular immunity.