ABSTRACT
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.
Subject(s)
Lymphoid Tissue , Memory T Cells , Child , Humans , Infant , CD8-Positive T-Lymphocytes , Immunologic Memory , Lymphoid Tissue/metabolism , Mucous Membrane , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/metabolism , Infant, Newborn , Child, PreschoolABSTRACT
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 transcriptional profiles enriched for lineage defining signatures and canonical functionality compared with blood, suggesting tissue as the primary site of Treg activity. Early life tonsil Tregs transcriptional profiles were further defined by pathways associated with activation, proliferation, and polyfunctionality. Observed differences in pediatric tonsil Treg transcriptional signatures were associated with phenotypic differences, high proliferative capacity, and robust production of IL-10 compared with adult Tregs. These results identify tissue as a major driver of Treg identity, provide new insights into developmental differences in Treg biology across the human lifespan, and demonstrate unique functional properties of early life Tregs.
Subject(s)
Palatine Tonsil , T-Lymphocytes, Regulatory , Humans , T-Lymphocytes, Regulatory/immunology , Palatine Tonsil/immunology , Palatine Tonsil/cytology , Child , Adult , Child, Preschool , Female , Male , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Transcriptome/immunology , Infant , Adolescent , Interleukin-10/immunology , CD8-Positive T-Lymphocytes/immunology , Gene Expression ProfilingABSTRACT
Indo-Gangetic Plains (IGP) experiences persistent and widespread rise of fog and haze during the winter season. This has been attributed to the rise in pollution levels and water vapor, but the reason for enhancement in latter is not clear yet. We detect moisture incursion from Arabian Sea, a phenomenon called atmospheric rivers (AR), land-falling intermittently along 12-25° N corridor of the west-coast of India during winter; using satellite and reanalysis data. The total vertically integrated horizontal water vapor transport in AR-landfalls ranging from 0.7 × 108 to 2.2 × 108 kg/s; nearly five-orders of magnitude larger than the average discharge of liquid water from Indus River into Arabian Sea. These AR events are playing prominent role in enhancing water vapor over IGP region by 19 ± 5%; in turn fueling the intensification of fog and haze through aerosol-water vapor interaction. We found that AR events enhanced aerosol optical depths over IGP by about 29 ± 13%. The progression of moist-laden winds in ARs onto Himalayan Mountains contributes to the precipitation that explains the observed rise in the extreme flow of western Himalayan Rivers in winter. We conclude that these ARs likely contribute to the decline of snow albedo as pollution-mixed-ARs encounter Hindukush-Karakoram-Himalayan mountain region.