Dendritic cells in the thymus contribute to T-regulatory cell induction

Abstract
Central tolerance is established through negative selection of self-reactive thymocytes and the induction of T-regulatory cells (TRs). The role of thymic dendritic cells (TDCs) in these processes has not been clearly determined. In this study, we demonstrate thatin vivo, TDCs not only play a role in negative selection but in the induction of TRs. TDCs include two conventional dendritic cell (DC) subtypes, CD8loSirpαhi/+(CD8loSirpα+) and CD8hiSirpαlo/−(CD8loSirpα), which have different origins. We found that the CD8hiSirpα+DCs represent a conventional DC subset that originates from the blood and migrates into the thymus. Moreover, we show that the CD8loSirpα+DCs demonstrate a superior capacity to induce TRsin vitro. Finally, using a thymic transplantation system, we demonstrate that the DCs in the periphery can migrate into the thymus, where they efficiently induce TRgeneration and negative selection.