Treg Cell Differentiation: From Thymus to Peripheral Tissue

Regulatory T cells (Tregs) are crucial mediators of self-tolerance in the periphery. They differentiate in the thymus, where interactions with thymus-resident antigen-presenting cells, an instructive cytokine milieu, and stimulation of the T cell receptor lead to the selection into the Treg lineage and the induction of Foxp3 gene expression. Once mature, Treg cells leave the thymus and migrate into either the secondary lymphoid tissues, e.g., lymph nodes and spleen, or peripheral nonlymphoid tissues. There is growing evidence that Treg cells go beyond the classical modulation of immune responses and also play important functional roles in nonlymphoid peripheral tissues. In this review, we summarize recent findings about the thymic Treg lineage differentiation as well as the further specialization of Treg cells in the secondary lymphoid and in the peripheral nonlymphoid organs.