Site-specific development and progressive maturation of human tissue resident memory T cells over infancy and childhood

Infancy and childhood are critical life stages for the generation of immune memory for protection against pathogens. This process has been challenging to elucidate in humans as most memory T cells reside in tissues. Here, we define localization, and developmental pathways of memory T cells in mucosal sites, lymphoid tissues, and blood from pediatric donors aged 0-10 years. We reveal that memory T cells preferentially localize in mucosal sites during infancy and accumulate more rapidly over childhood compared to blood and lymphoid organs. Mucosal memory T cells in infancy exhibit stem-like transcriptional profiles, but progressively adopt signatures of mature tissue resident memory T cells over childhood. Our results show that exposures during the formative years establish the landscape of immunity through tissue-specific generation and adaptation of memory T cells Resident memory T cells over infancy and childhood