Journal
IMMUNITY
Volume 44, Issue 4, Pages 847-859Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2016.01.025
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Funding
- R01 [R01CA160371, R01AI110507, R01CA166770]
- Cancer Research Institute Investigator Award
- University of Chicago Comprehensive Cancer Center
- NIH/NCI F31 predoctoral fellowship [CA183357]
- MSKCC Comprehensive Cancer Center [P30 CA008748]
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Although antigen recognition mediated by the T cell receptor (TCR) influences many facets of Foxp3(+) regulatory T (Treg) cell biology, including development and function, the cell types that present antigen to Treg cells in vivo remain largely undefined. By tracking a clonal population of Aire-dependent, prostate-specific Treg cells in mice, we demonstrated an essential role for dendritic cells (DCs) in regulating organ-specific Treg cell biology. We have shown that the thymic development of prostate-specific Treg cells required antigen presentation by DCs. Moreover, Batf3-dependent CD8 alpha(+) DCs were dispensable for the development of this clonotype and had negligible impact on the polyclonal Treg cell repertoire. In the periphery, CCR7-dependent migratory DCs coordinated the activation of organ-specific Treg cells in the prostate-draining lymph nodes. Our results demonstrate that the development and peripheral regulation of organ-specific Treg cells are dependent on antigen presentation by DCs, implicating DCs as key mediators of organ-specific immune tolerance.
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