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

• Published in: Nature immunology Vol. 2; no. 4; pp. 301 - 306
• Main Authors: Caton, Andrew J, Jordan, Martha S, Boesteanu, Alina, Reed, Amy J, Petrone, Andria L, Holenbeck, Andrea E, Lerman, Melissa A, Naji, Ali
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-04-2001
• Subjects: Amino Acid Sequence; Animals; Autoantigens - genetics; CD4-Positive T-Lymphocytes - classification; CD4-Positive T-Lymphocytes - immunology; Mice; Mice, Inbred BALB C; Mice, Transgenic; Peptides; Phenotype; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Receptors, Interleukin-2 - metabolism; Self Tolerance; Thymus Gland - cytology; Thymus Gland - immunology
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/86302

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.