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


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
2008-12-16
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Journal Article
105
50
19869-19874
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.
NATL ACAD SCIENCES
IMMUNOLOGICAL SELF-TOLERANCE; TRANSCRIPTION FACTOR FOXP3; STEADY-STATE CONDITIONS; CLASS-II MOLECULES; MOUSE THYMUS; CLONAL DELETION; POSITIVE SELECTION; EPITHELIAL-CELLS; SURFACE-MARKERS; LYMPHOID ORGANS
10.1073/pnas.0810268105
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