Regulatory T cell development in the thymus

Development of a comprehensive regulatory T (Treg) cell compartment in the thymus is required to maintain immune homeostasis and prevent autoimmunity. In this study, we review cellular and molecular determinants of T_reg cell development in the thymus. We focus on the evidence for a self-antigen-focused T_reg cell repertoire as well as the APCs responsible for presenting self-antigens to developing thymocytes. We also cover the contribution of different cytokines to thymic T_reg development and the cellular populations that produce these cytokines. Finally, we update the originally proposed "two-step" model of thymic T_reg differentiation by incorporating new evidence demonstrating that T_reg cells develop from two T_reg progenitor populations and discuss the functional importance of T_reg cells generated via either progenitor pathway.