Thymocyte deletion can bias regulatory T cell formation toward low abundance self-peptide

Autoreactive CD4+ T cells can undergo deletion and/or become CD25+Foxp3+ Treg cells as they develop intrathymically, but how these alternative developmental fates are specified based on interactions with self-peptide(s) is not understood. We show here that thymocytes expressing an autoreactive TCR can be subjected to varying degrees of deletion that correlate with the amount of self-peptide. Strikingly, among thymocytes that evade deletion, similar proportions acquire Foxp3 expression. These findings provide evidence that Foxp3+ Treg cells can develop among members of a cohort of autoreactive thymocytes that have evaded deletion by a self-peptide, and that deletion and Treg cell formation can act together to bias the Treg cell repertoire toward low abundance self-peptide(s).