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...

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Published in:Immunity (Cambridge, Mass.) Mass.), 2023-08, Vol.56 (8), p.1894-1909.e5
Main Authors: Connors, Thomas J, Matsumoto, Rei, Verma, Shivali, Szabo, Peter A, Guyer, Rebecca, Gray, Joshua, Wang, Zicheng, Thapa, Puspa, Dogra, Pranay, Poon, Maya M L, Rybkina, Ksenia, Bradley, Marissa C, Idzikowski, Emma, McNichols, James, Kubota, Masaru, Pethe, Kalpana, Shen, Yufeng, Atkinson, Mark A, Brusko, Maigan, Brusko, Todd M, Yates, Andrew J, Sims, Peter A, Farber, Donna L
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:1074-7613
1097-4180
1097-4180
DOI:10.1016/j.immuni.2023.06.008