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 thymocytes 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.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1111/sji.12681 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!