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 generating immune memory to protect against pathogens; however, the timing, location, and pathways for memory development in humans remain elusive. Here, we investigated T cells in mucosal sites, lymphoid tissues, and blood from 96 pediatric donors aged 0–10 years using phenotypic, functional, and transcriptomic profiling. Our results revealed that memory T cells preferentially localized in the intestines and lungs during infancy and accumulated more rapidly in mucosal sites compared with blood and lymphoid organs, consistent with site-specific antigen exposure. Early life mucosal memory T cells exhibit distinct functional capacities and stem-like transcriptional profiles. In later childhood, they progressively adopt proinflammatory functions and tissue-resident signatures, coincident with increased T cell receptor (TCR) clonal expansion in mucosal and lymphoid sites. Together, our findings identify staged development of memory T cells targeted to tissues during the formative years, informing how we might promote and monitor immunity in children. [Display omitted] • Memory T cells preferentially accumulate in human mucosal tissues during early life • T RM cells undergo functional maturation over childhood • T RM cells exhibit distinct transcriptional programs and site-specific expansion over age Immune memory generation during early childhood is critical for long-term protective immunity. Connors et al. analyze the development of human memory T cells in lymphoid organs, mucosal sites, and blood over infancy and childhood. Memory T cells accumulate rapidly in the intestines and lungs and display age- and tissue-driven maturation stages. [ABSTRACT FROM AUTHOR]