Dendritic Cells Coordinate the Development and Homeostasis of Organ-Specific Regulatory T Cells

Although antigen recognition mediated by the T cell receptor (TCR) influences many facets of Foxp3+ regulatory T (Treg) cell biology, including development and function, the cell types that present antigen to Treg cells in vivo remain largely undefined. By tracking a clonal population of Aire-dependent, prostate-specific Treg cells in mice, we demonstrated an essential role for dendritic cells (DCs) in regulating organ-specific Treg cell biology. We have shown that the thymic development of prostate-specific Treg cells required antigen presentation by DCs. Moreover, Batf3-dependent CD8α+ DCs were dispensable for the development of this clonotype and had negligible impact on the polyclonal Treg cell repertoire. In the periphery, CCR7-dependent migratory DCs coordinated the activation of organ-specific Treg cells in the prostate-draining lymph nodes. Our results demonstrate that the development and peripheral regulation of organ-specific Treg cells are dependent on antigen presentation by DCs, implicating DCs as key mediators of organ-specific immune tolerance. [Display omitted] •DCs coordinate the thymic development of Aire-dependent prostate-specific Treg cells•Loss of CD8α+ DCs has negligible impact on the thymic polyclonal Treg cell repertoire•Antigen is continuously required for the activation of prostate-specific Treg cells•CCR7-dependent migratory DCs regulate prostate-specific Treg cells in the lymph nodes The identity of the antigen-presenting cells that orchestrate the thymic development and peripheral homeostasis of organ-specific regulatory T cells remains unclear. Savage and colleagues demonstrate a critical role for dendritic cells in coordinating these processes for a naturally occurring clonal population of regulatory T cells reactive to a prostate-specific antigen.