Intestinal CD8αα IELs derived from two distinct thymic precursors have staggered ontogeny.

CD8 alpha alpha intraepithelial lymphocytes (IELs) are abundant T cells that protect the gut epithelium. Their thymic precursors (IELps) include PD-1(+)( )type A and Tbet(+) type B populations, which differ in their antigen-receptor specificities. To better understand CD8 alpha alpha IEL ontogeny, we performed "time-stamp" fate mapping experiments and observed that it seeds the intestine predominantly during a narrow time window in early life. Adoptively transferred IELps parked better in the intestines of young mice than in adults. In young mice, both type A and type B IELps had an S1PR1(+) and alpha 4 beta 7(+) emigration- and mucosal-homing competent phenotype, while this was restricted to type A IELps in adults. Only CD8 alpha alpha IELs established in early life were enriched in cells bearing type B IELp TCR usage. Together, our results suggest that the young intestine facilitates CD8 alpha alpha IEL establishment and that early IELs are distinct from IELs established after this initial wave. These data provide novel insight into the ontogeny of CD8 alpha alpha IELs.