Distinct recirculation potential of CD69+CD103- and CD103+ thymic memory CD8+ T cells.

Tissue-resident memory T (TRM) cells occupy peripheral and lymphoid tissues where they confer protection against local infection. While epithelial CD8+ TRM cells coexpress CD69 and CD103, CD103- memory cells have been described in various organs and are often presumed non-recirculating based on their expression of CD69. We found that both CD69+CD103+ and CD69+CD103- memory cells populated the thymus upon transfer of CD8+ effector T cells into uninfected recipients. Transcriptionally and phenotypically, CD103+ thymic cells resembled non-lymphoid TRM cells, whereas CD69+CD103- cells displayed a profile that was more closely related to recirculating cells. Although CD69 was required for optimal CD103+ TRM formation, its expression alone did not identify permanently resident cells, as CD69+CD103- cells disappeared from the thymus following antibody-mediated depletion of recirculating cells. Our findings highlight a distinct migration potential of phenotypically divergent thymic CD8+ memory T cells and emphasise the inadequacy of CD69 as a marker of tissue residency.