Antigen-Specific Development of Mucosal Foxp3+ROR{gamma}t+ T Cells from Regulatory T Cell Precursors [IMMUNE REGULATION]

Foxp3⁺retinoic acid–related orphan receptor (ROR)t⁺ T cells have recently been characterized as an immunoregulatory population highly enriched in the colon lamina propria. However, their developmental origin and relationship to RORt^– 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⁺RORt⁺ 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⁺RORt⁺ cells to regulate Th17 immunity. Naive transgenic T cells expressing a Foxp3⁺RORt⁺-restricted TCR first acquire a Foxp3⁺RORt^– phenotype before coexpressing RORt, suggesting that Foxp3⁺RORt⁺ cell development can occur via an RORt^– regulatory T cell intermediate.

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