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 Treg cell development in the thymus. We focus on the evidence for a self-antigen-focused Treg 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 Treg development and the cellular populations that produce these cytokines. Finally, we update the originally proposed "two-step" model of thymic Treg differentiation by incorporating new evidence demonstrating that Treg cells develop from two Treg progenitor populations and discuss the functional importance of Treg cells generated via either progenitor pathway.
Copyright © 2019 by The American Association of Immunologists, Inc.