Thymic regulatory T cell niche size is dictated by limiting IL-2 from antigen-bearing dendritic cells and feedback competition.
The thymic production of regulatory T cells (Treg cells) requires interleukin 2 (IL-2) and agonist T cell antigen receptor (TCR) ligands and is controlled by competition for a limited developmental niche, but the thymic sources of IL-2 and the factors that limit access to the niche are poorly understood. Here we found that IL-2 produced by antigen-bearing dendritic cells (DCs) had a key role in Treg cell development and that existing Treg cells limited new development of Treg cells by competing for IL-2. Our data suggest that antigen-presenting cells (APCs) that can provide both IL-2 and a TCR ligand constitute the thymic niche and that competition by existing Treg cells for a limited supply of IL-2 provides negative feedback for new production of Treg cells.
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA.
Brian M
BM
Weist
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA.
Nadia
N
Kurd
Ecole Normale Supérieure, Paris, France.
Jeremy
J
Boussier
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA.
Shiao Wei
SW
Chan
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA.
Ellen A
EA
Robey
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D002454:Cell Differentiation; D002460:Cell Line; D060833:Cellular Microenvironment; D003713:Dendritic Cells / Q000502:physiology*; D025461:Feedback, Physiological; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000819:agonists*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D013950:Thymus Gland / Q000276:immunology*
D000941:Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell