Nature Immunology
2, 301 - 306 (2001)
doi:10.1038/86302
Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptideMartha S. Jordan1, Alina Boesteanu1, Amy J. Reed1, Andria L. Petrone1, Andrea E. Holenbeck1, Melissa A. Lerman1, Ali Naji2
& Andrew J. Caton11
The Wistar Institute, Philadelphia, PA 19104, USA. 2
University of Pennsylvania, Department of Surgery, Philadelphia, PA 19104, USA.
Correspondence should be addressed to Andrew J. Caton caton@wistar.upenn.eduDespite 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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