Article abstract
Nature Immunology 10, 610 - 617 (2009)
Published online: 10 May 2009 | doi:10.1038/ni.1739
Intraclonal competition limits the fate determination of regulatory T cells in the thymus
Jhoanne L Bautista1, Chan-Wang J Lio1, Stephanie K Lathrop1, Katherine Forbush2, Yuqiong Liang2,4, Jingqin Luo3, Alexander Y Rudensky2,4 & Chyi-Song Hsieh1
Abstract
Because the deletion of self-reactive T cells is incomplete, thymic development of natural Foxp3+CD4+ regulatory T cells (Treg cells) is required for preventing autoimmunity. However, the function of T cell antigen receptor (TCR) specificity in thymic Treg cell development remains controversial. To address this issue, we generated a transgenic line expressing a naturally occurring Treg cell–derived TCR. Unexpectedly, we found that efficient thymic Treg cell development occurred only when the antigen-specific Treg cell precursors were present at low clonal frequency (<1%) in a normal thymus. Using retroviral vectors and bone marrow chimeras, we observed similar activity with two other Treg cell–derived TCRs. Our data demonstrate that thymic Treg cell development is a 'TCR-instructive' process involving a niche that can be saturable at much lower clonal frequencies than is the niche for positive selection.
- Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri, USA.
- Howard Hughes Medical Institute and Department of Immunology, University of Washington, Seattle, Washington, USA.
- Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA.
- Present addresses: Center for Hepatitis Research, University of Texas Medical Branch, Galveston, Texas, USA (Y.L.) and Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA (A.Y.R.).
Correspondence to: Chyi-Song Hsieh1 e-mail: chsieh@dom.wustl.edu
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