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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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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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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DOI: https://doi.org/10.1038/86302
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