Thymic origin of intestinal αβ T cells revealed by fate mapping of RORγt+ cells

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 expressing the alphabeta T cell receptor are derived from precursors that express RORgammat, an orphan nuclear hormone receptor detected only in immature CD4(+) CD8(+) thymocytes, fetal lymphoid tissue-inducer (LTi) cells, and LTi-like cells in crypto-patches within the adult intestinal lamina propria. Using cell fate mapping, we found that all intestinal alphabeta T cells are progeny of CD4(+) CD8(+) thymocytes, indicating that the adult intestine is not a significant site for alphabeta T cell development. Our results suggest that intestinal RORgammat(+) cells are local organizers of mucosal lymphoid tissue.