Thymic Origin of Intestinal αß T Cells Revealed by Fate Mapping of RORγt + Cells

Abstract

Intestinal intraepithelial T lymphocytes (IELs) are likely to play a key role in host mucosal immunity and, unlike other T cells, have been proposed to differentiate from local precursors rather than from thymocytes. We show here that IELs expressingthe αβ T cell receptor are derived from precursors that express RORγt, an orphan nuclear hormone receptor detected only in immature CD4 + CD8 + thymocytes, fetal lymphoid tissue–inducer (LTi) cells, and LTi-like cells in cryptopatches within the adult intestinal lamina propria. Using cell fate mapping, we found that all intestinal αβ T cells are progeny of CD4 + CD8 + thymocytes, indicatingthat the adult intestine is not a significant site for αβ T cell development. Our results suggest that intestinal RORγt + cells are local organizers of mucosal lymphoid tissue.