Common gamma chain cytokines promote regulatory T cell development and survival at the CD4 + CD8 + stage in the human thymus.

Thymic commitment of human FOXP3+ regulatory T cells begins at the double positive (DP) CD4+ CD8+ stage. In the current study we show that interleukin-2 promotes the development of FOXP3+ thymocytes and enhances their survival at the DP phase. IL-2 increases the frequency of FOXP3+ cells and promotes the Treg phenotype after TCR-mediated positive selection at the most mature DP stage. However, it has no effect on FOXP3+ cells at the earlier maturation steps before positive selection. DP FOXP3+ are highly susceptible to cell death but IL-2 promotes their survival. The anti-apoptotic protein BCL-2 (B Cell Lymphoma 2) is also upregulated by IL-2 at the most mature DP stage. In addition to IL-2, we identify IL-15 to have a significant role in the upregulating FOXP3 and survival of Tregs at the DP phase. IL-7 also increases the expression of BCL-2 in the DP FOXP3+ thymocytes. Our results indicate that common gamma chain cytokines IL-2, IL-7 and IL-15 promote the development of regulatory T cells at the most mature DP stage after TCR-mediated positive selection through suppressing cell death. This article is protected by copyright. All rights reserved.