Fig. 1.

Regulatory T cell development (Churlaud et al. 2015; Josefowicz and Rudensky 2009; Kosten and Rustemeyer 2015; Zhang et al. 2014). Thymus-derived regulatory T cells (tTregs) can develop from SP CD4⁺CD8⁻ thymocytes (a), or an alternative pathway of their development from DN is hypothesized (b); CD8⁺CD25⁺Foxp3⁺ Tregs can also arise in the thymus from SP CD8⁺CD4⁻ thymocytes (c). Both thymic Tregs migrate to peripheral lymphoid organs as mature T cells exhibiting suppressive potential. Peripherally induced Tregs differentiate from antigen-activated naive Th CD4⁺ cells into pTregs of CD4⁺CD25⁺Foxp3⁺ phenotype. Additionally, Tr1 and Th3 are generated (d); naive T CD8⁺ cells can differentiate into CD8⁺CD28⁻ Tregs (e); γδ Tregs can arise from antigen-activated γδ T cells (f). DN double-negative, DP double-positive, SP single-positive, TEC thymic epithelial cells, DC dendritic cells