Thymic selection of CD4(+)CD25(+) regulatory T cells induced by an agonistself-peptide

Despite accumulating evidence that regulatory T cells play a crucial role i n preventing autoimmunity, the processes underlying their generation during immune repertoire formation are unknown. We show here that interactions wi th 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 wi th high affinity for a self peptide because thymocytes that bear TCRs with low affinity do not undergo selection into this pathway. Our findings indic ate that specificity for self-peptides directs the selection of CD4(+)CD25( +) regulatory thymocytes by a process that is distinct from positive select ion and deletion.