Weaning imprints a hybrid cytotoxic-regulatory identity on intestinal CD4+ T lymphocytes

Weaning imprints a transient cytotoxic-regulatory hybrid identity in intestinal lamina propria CD4+ T cells, with granzyme B expression microbiota-dependent only in the ileum.

• Why it matters: The neonatal gut transitions from milk to solid food and becomes densely colonized, but how the intestinal T cell compartment is established during this window is unclear.
• What they did: Using fate-mapping to timestamp naive T cells from suckling to adulthood, the study combined imaging, transcriptomic, and repertoire analyses, including germ-free mice.
• The result: Intestinal T cell entry peaked at weaning, and clonal expansions at weaning were restricted to the small intestinal lamina propria and absent in germ-free mice, with most expanded clones recognizing early-life commensals.