TY - JOUR
T1 - Dendritic cells in the thymus contribute to T-regulatory cell induction
AU - Proietto, Anna I
AU - van Dommelen, Serani LH
AU - Zhou, Penghui
AU - Rizzitelli, Alexandra
AU - D'Amico, Angela
AU - Steptoe, Raymond J
AU - Naik, Shalin H.
AU - Lahoud, Mireille H.
AU - Liu, Yang
AU - Zheng, Pan
AU - Shortman, Ken
AU - Wu, Li
PY - 2008/12/16
Y1 - 2008/12/16
N2 - Central tolerance is established through negative selection of self-reactive thymocytes and the induction of T-regulatory cells (T Rs). 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 Rs. TDCs include two conventional dendritic cell (DC) subtypes, CD8loSirpαhi/+ (CD8loSirpα +) and CD8hiSirpαlo/- (CD8 loSirpα-), 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 TRs 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 TR generation and negative selection.
AB - Central tolerance is established through negative selection of self-reactive thymocytes and the induction of T-regulatory cells (T Rs). 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 Rs. TDCs include two conventional dendritic cell (DC) subtypes, CD8loSirpαhi/+ (CD8loSirpα +) and CD8hiSirpαlo/- (CD8 loSirpα-), 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 TRs 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 TR generation and negative selection.
KW - Migratory dendritic cells
KW - Thymic selection
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=58149376454&partnerID=8YFLogxK
U2 - 10.1073/pnas.0810268105
DO - 10.1073/pnas.0810268105
M3 - Article
C2 - 19073916
AN - SCOPUS:58149376454
VL - 105
SP - 19869
EP - 19874
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 50
ER -