Interleukin-2 drives immature double negative thymocytes into γδ T cells expressing Foxp3 on a stromal cell line in vitro

γδ T cells are exported from the thymus as innate-like lymphocytes that can immediately respond to antigens. In the thymus, γδ T cells diverge into functionally distinct lineages. It is not known whether γδ T cells differentiate into regulatory cells that express Foxp3, which is an essential transcription factor for CD4+ regulatory T cells. In this study, we analyzed CD25+ immature thymocytes that give rise to both αβ and γδ thymocytes. These precursor cells have the potential to differentiate into Foxp3+ γδ T cells on a stromal cell line, TSt4-Dll1. Development of Foxp3+ γδ thymocytes in this culture was dependent on IL-2. IL-2 stimulation induced Id3, Egr1, and Egr3 expression in CD25+ immature thymocytes, suggesting that it could activate signaling molecules that are downstream of TCR signaling. The induction of Foxp3 in precursor γδ T cells suggested that IL-2 could activate the Foxp3 gene early in thymocyte development.