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Weaning imprints a hybrid cytotoxic-regulatory identity on intestinal CD4+ T lymphocytes
M. Schernthanner, R. Gokhale, A. Thoms, G. L. dos Reis, M. Saad, M. M. Clark, Y. S. Yin, I. Mamede, B. S. Reis, T. B. R. Castro, R. Parsa, E. Fuchs, D. Mucida, A. M. Bilate
Résumé : The intestinal immune system must adapt as the neonatal gut shifts from milk to solid food and becomes densely colonized. How the T cell compartment is established under these conditions remains unclear. Using fate-mapping to timestamp naive T cells, with imaging, transcriptomic, and repertoire analyses, we tracked them from suckling to adulthood. Intestinal T cell entry peaked at weaning, coinciding with relocation from crypts to villi guided by the tissue microenvironment and, partly, the microbiota. T cells timestamped at suckling persisted into adulthood and, at weaning, adopted a transient cytotoxic-regulatory state in the lamina propria, with granzyme B expression microbiota-dependent only in the ileum. Clonal expansions at weaning were restricted to the small intestinal lamina propria and absent in germ-free mice. Most expanded clones recognized early-life commensals. Weaning is a physiological window of transient inflammation imprinting a hybrid CD4 T cell compartment, suggesting that early-life commensals modulate T cell selection.