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

Immunity. 2023 Aug 8;56(8):1894-1909.e5. doi: 10.1016/j.immuni.2023.06.008. Epub 2023 Jul 7.


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.

Keywords: T cells; developmental immunity; human immunology; infant immunity; mucosal immunity; tissue-resident memory T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Child
  • Child, Preschool
  • Humans
  • Immunologic Memory
  • Infant
  • Infant, Newborn
  • Lymphoid Tissue* / metabolism
  • Memory T Cells*
  • Mucous Membrane
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism


  • Receptors, Antigen, T-Cell