biostudies-literatureVerma SHHS | NIH | NIH Office of the DirectorHHS | NIH | NIH Office of the Director (OD)NCATS NIH HHSNCRR NIH HHSNIAID NIH HHSHHS | NIH | National Center for Advancing Translational Sciences (NCATS)HHS | NIH | National Center for Research ResourcesHHS | NIH | National Institute of Allergy and Infectious DiseasesHHS | NIH | National Center for Research Resources (NCRR)HHS | NIH | National Center for Advancing Translational SciencesNIH HHSHHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)306-316https://www.ebi.ac.uk/biostudies/studies/S-EPMC11304551biostudies-literatureUnknown213(3)CD4+ regulatory T cells (Tregs) are key orchestrators of the immune system, fostering the establishment of protective immunity while preventing deleterious responses. Infancy and childhood are crucial periods of rapid immunologic development, but how Tregs mediate immune responses at these earliest timepoints of human life is poorly understood. In this study, we compare blood and tissue (tonsil) Tregs across pediatric and adult subjects to investigate age-related differences in Treg biology. We observed increased FOXP3 expression and proportions of Tregs in tonsil compared with paired blood samples in children. Within tonsil, early life Tregs accumulated in extrafollicular regions with cellular interactions biased toward CD8+ T cells. Tonsil Tregs in both children and adults expressed tranJournal of immunology (Baltimore, Md. : 1950)Distinct Localization, Transcriptional Profiles, and Functionality in Early Life Tonsil Regulatory T Cells.PMC11304551S10RR027050P01 AI106697UL1 TR001873K23AI141686S10 OD030282UL1TR001873S10OD020056K23 AI141686S10 OD020056S10 RR027050P01AI106697U01AI100119U01 AI100119Verma SGray JBradley MCGrunstein EPethe KDogra PMaurrasse SWaldman EConnors TJCaron DPJang MFarber DLfalseDistinct Localization, Transcriptional Profiles, and Functionality in Early Life Tonsil Regulatory T Cells.CD4+ regulatory T cells (Tregs) are key orchestrators of the immune system, fostering the establishment of protective immunity while preventing deleterious responses. Infancy and childhood are crucial periods of rapid immunologic development, but how Tregs mediate immune responses at these earliest timepoints of human life is poorly understood. In this study, we compare blood and tissue (tonsil) Tregs across pediatric and adult subjects to investigate age-related differences in Treg biology. We observed increased FOXP3 expression and proportions of Tregs in tonsil compared with paired blood samples in children. Within tonsil, early life Tregs accumulated in extrafollicular regions with cellular interactions biased toward CD8+ T cells. Tonsil Tregs in both children and adults expressed tran2024-01-01T00:00:00Z2024 Aug2026-03-17T15:27:39.095Z2025-08-16T03:06:51.281ZS-EPMC113045513890511010.4049/jimmunol.2300890