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

Authors: Anna I. Proietto, Serani van Dommelen, Penghui Zhou, Alexandra Rizzitelli, Angela D’Amico, Raymond J. Steptoe, Shalin H. Naik, Mireille H. Lahoud, Yang Liu, Pan Zheng, Ken Shortman, Li Wu - Proceedings of the National Academy of Sciences, PNAS 2008 cited by 302

Central tolerance is established through negative selection of self-reactive thymocytes and the induction of T-regulatory cells (T(R)s). The role of thymic dendritic cells (TDCs) in these processes has not been clearly determined. In this study, we demonstrate that in vivo, TDCs not only play a role in negative selection but in the induction of T(R)s. TDCs include two conventional dendritic cell (DC) subtypes, CD8(lo)Sirpalpha(hi/+) (CD8(lo)Sirpalpha(+)) and CD8(hi)Sirpalpha(lo/-) (CD8(hi)Sirpalpha(-)) [corrected] which have different origins. We found that the CD8(hi)Sirpalpha(+) DCs represent a conventional DC subset that originates from the blood and migrates into the thymus. Moreover, we show that the CD8(lo)Sirpalpha(+) DCs demonstrate a superior capacity to induce T(R)s in vitro. Finally, using a thymic transplantation system, we demonstrate that the DCs in the periphery can migrate into the thymus, where they efficiently induce T(R) generation and negative selection.