150 Skin CD69+CD62L+ TRM, a Subset with Renewal Capacity Gives Rise to CD103+CD49a+ TRM

Tissue-resident memory T cells (TRM) are seeded and persist for years at the site of inflammatory responses in non-lymphoid tissues. In human skin, enrichment of oligoclonal cytotoxic CD103+CD49a+ TRM in disequilibrium with circulating T cells indicates local renewal of epidermal T cells. Indeed, a subset of less differentiated skin resident CD62L+CD49a- CD103-CD69+ TRM cells was identified by single cell CITE-seq and T cell receptor sequencing. Resident CD62L+ CD69+ T cells showed clonal sharing with epidermal CD49a+ CD103+ CD69+ cytotoxic T cells. Following stimulation, CD62L+ CD69+ T cells displayed high proliferation potential and differentiated into cytotoxic CD103+ CD49a+ TRM cells. Furthermore, in cutaneous T cell lymphoma (CTCL), driven by one expanded clone of malignant CD8+ T cells, both lowly differentiated CD69+CD62L+ T cells and highly differentiated CD49a+CD103+ TRM cells phenotypes were detected in the malignant clone. In conclusion, we revealed a skin resident precursor population to CD49a+CD103+ TRM cells marked by the expression of CD69 and CD62L, capable of maintaining the local pool of skin resident memory T cells in health and skin diseases.