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Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide

Nature Immunology volume 2, pages 301–306 (2001)Cite this article

An Erratum to this article was published on 01 May 2001

Abstract

Despite accumulating evidence that regulatory T cells play a crucial role in preventing autoimmunity, the processes underlying their generation during immune repertoire formation are unknown. We show here that interactions with a single self-peptide can induce thymocytes that bear an autoreactive T cell receptor (TCR) to undergo selection to become CD4+CD25+ regulatory T cells. Selection of CD4+CD25+ thymocytes appears to require a TCR with high affinity for a self peptide because thymocytes that bear TCRs with low affinity do not undergo selection into this pathway. Our findings indicate that specificity for self-peptides directs the selection of CD4+CD25+ regulatory thymocytes by a process that is distinct from positive selection and deletion.

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Figure 1: CD4+CD25+ S1–specific T cells are generated intrathymically.
Figure 2: CD4+CD25+ regulatory T cells in TS1×HA28 mice are selected by radioresistant thymic elements and are not dependent upon allelic inclusion of endogenous TCR chains.
Figure 3: Phenotypic changes accompanying CD4+CD25+ regulatory thymocyte development.
Figure 4: Thymocytes that express a low affinity TCR are not selected to become CD25+ T cells.

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Acknowledgements

We thank H. M. Guay and C. L. Iacocca for assistance; Jeffrey Faust for cell sorting; the University of Pennsylvania Flow Cytometry and Cell Sorting Facility for help with five-color flow cytometry; and M. P. Riley, J. A. Punt and T. M. Laufer for helpful discussions. Supported by National Institutes of Health grants AI24541, CA10815, 5T32AR07442 and 5T32EY07131.

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  1. The Wistar Institute, Philadelphia, 19104, PA, USA

    Martha S. Jordan, Alina Boesteanu, Amy J. Reed, Andria L. Petrone, Andrea E. Holenbeck, Melissa A. Lerman & Andrew J. Caton

  2. Department of Surgery, University of Pennsylvania, Philadelphia, 19104, PA, USA

    Ali Naji

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Correspondence to Andrew J. Caton.

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Jordan, M., Boesteanu, A., Reed, A. et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol 2, 301–306 (2001). https://doi.org/10.1038/86302

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