Abstract

Foxp3+retinoic acid–related orphan receptor (ROR)γt+ T cells have recently been characterized as an immunoregulatory population highly enriched in the colon lamina propria. However, their developmental origin and relationship to RORγt regulatory T and Th17 cells remain unclear. In this study, we use a fixed TCRβ system to show that the TCR repertoire of the Foxp3+RORγt+ population is mostly distinct compared with other colonic T cell subsets. However, of these TCRs, a fraction is also found in the Th17 subset, suggesting that TCR repertoire overlap may contribute to the reported ability of Foxp3+RORγt+ cells to regulate Th17 immunity. Naive transgenic T cells expressing a Foxp3+RORγt+-restricted TCR first acquire a Foxp3+RORγt phenotype before coexpressing RORγt, suggesting that Foxp3+RORγt+ cell development can occur via an RORγt regulatory T cell intermediate.

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