Dendritic cells coordinate the development and homeostasis of organ-specific regulatory T cells (LYM2P.730)

Abstract Foxp3+ regulatory T cells (Tregs) are critical for the maintenance of tolerance to self. However, the antigen presenting cells (APCs) controlling the thymic development and peripheral homeostasis of these cells have yet to be clearly defined. Previously, we identified a monoclonal population of prostate-specific Tregs, termed MJ23 Tregs, that require Autoimmune Regulator (Aire) for their thymic development. Using a variety of mixed bone marrow chimera experiments, we sought to determine the contributions of various thymic APC subsets towards MJ23 Treg development. We demonstrate that the thymic development of MJ23 Tregs requires both MHC-II and B7.1/.2 on bone-marrow derived cells. Moreover, development is abolished by the depletion of CD11c-expressing cells. Together, these data indicate that the antigen recognized by MJ23 Tregs in the thymus must be transferred from Aire-expressing medullary thymic epithelial cells to CD11c-expressing dendritic cells to coordinate MJ23 Treg development. In the periphery, we demonstrate that the depletion of CD11c-expressing cells eliminates the enrichment of MJ23 Tregs in the prostate-draining lymph nodes, demonstrating that dendritic cells also coordinate the anatomical distribution of organ-specific Tregs in the secondary lymphoid organs. In all, our results reveal a critical role for dendritic cells in orchestrating the development and homeostasis of Aire-dependent, organ-specific Treg cells.