4.7 Article

Thymic regulatory T cell niche size is dictated by limiting IL-2 from antigen-bearing dendritic cells and feedback competition

Journal

NATURE IMMUNOLOGY
Volume 16, Issue 6, Pages 635-+

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3171

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Funding

  1. US National Institutes of Health [R01AI064227, T32AI100829]

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The thymic production of regulatory T cells (T-reg 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 T-reg cell development and that existing T-reg cells limited new development of T-reg 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 T-reg cells for a limited supply of IL-2 provides negative feedback for new production of T-reg cells.

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