gamma delta T cells are exported from the thymus as innate-like lymphocytes that can immediately respond to antigens. In the thymus, gamma delta T cells diverge into functionally distinct lineages. It is not known whether gamma delta 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 alpha beta and gamma delta thymocytes. These precursor cells have the potential to differentiate into Foxp(3+) gamma delta T cells on a stromal cell line, TSt4-Dll1. Development of Foxp(3+) gamma delta 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 gamma delta T cells suggested that IL-2 could activate the Foxp3 gene early in thymocyte development. (C) 2014 Elsevier Inc. All rights reserved.