Dendritic cells in the thymus contribute to T-regulatory cell induction
- Author(s)
- Proietto, AI; van Dommelen, S; Zhou, PH; Rizzitelli, A; D'Amico, A; Steptoe, RJ; Naik, SH; Lahoud, MH; Liu, Y; Zheng, P; Shortman, K; Wu, L;
- Details
- Publication Year 2008-12-16,Volume 105,Issue #50,Page 19869-19874
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- 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)Sirp alpha(hi/+) (CD8(lo)Sirp alpha(+)) and CD8(hi)Sirp alpha lo/(-) (CD8(lo)Sirp alpha(-)), which have different origins. We found that the CD8(hi)Sirp alpha(+) DCs represent a conventional DC subset that originates from the blood and migrates into the thymus. Moreover, we show that the CD8(lo)Sirp alpha(+) 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 T(R) generation and negative selection.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- IMMUNOLOGICAL SELF-TOLERANCE; TRANSCRIPTION FACTOR FOXP3; STEADY-STATE CONDITIONS; CLASS-II MOLECULES; MOUSE THYMUS; CLONAL DELETION; POSITIVE SELECTION; EPITHELIAL-CELLS; SURFACE-MARKERS; LYMPHOID ORGANS
- Publisher's Version
- https://doi.org/10.1073/pnas.0810268105
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2008-12-16 12:00:00