Specific niches for lung-resident memory CD8(+) T cells at the site of tissue regeneration enable CD69-independent maintenance

CD8(+) tissue-resident memory T cells (T(RM) cells) reside permanently in nonlymphoid tissues and provide a first line of protection against invading pathogens. However, the precise localization of CD8(+) T(RM) cells in the lung, which physiologically consists of a markedly scant interstitium compared with other mucosa, remains unclear. In this study, we show that lung CD8(+) T(RM) cells localize predominantly in specific niches created at the site of regeneration after tissue injury, whereas peripheral tissue-circulating CD8(+) effector memory T cells (T(EM) cells) are widely but sparsely distributed in unaffected areas. Although CD69 inhibited sphingosine 1–phosphate receptor 1–mediated egress of CD8(+) T cells immediately after their recruitment into lung tissues, such inhibition was not required for the retention of cells in the T(RM) niches. Furthermore, despite rigid segregation of T(EM) cells from the T(RM) niche, prime-pull strategy with cognate antigen enabled the conversion from T(EM) cells to T(RM) cells by creating de novo T(RM) niches. Such damage site–specific localization of CD8(+) T(RM) cells may be important for efficient protection against secondary infections by respiratory pathogens.