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.
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Acknowledgements
We thank N. Santacruz and J. Hunn for technical assistance, and K. Murphy, W. Yokoyama, P. Allen, W. Swat, J. Scott-Brown and J. Fontenot for discussions and critical review of the manuscript. Supported by the Arthritis Foundation, Burroughs Wellcome Fund and the US National Institutes of Health (C.-S.H.).
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Bautista, J., Lio, CW., Lathrop, S. et al. Intraclonal competition limits the fate determination of regulatory T cells in the thymus. Nat Immunol 10, 610–617 (2009). https://doi.org/10.1038/ni.1739
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DOI: https://doi.org/10.1038/ni.1739
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