Thymocyte deletion can bias Treg formation toward low‐abundance self‐peptide

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Abstract
Autoreactive CD4+ T cells can undergo deletion and/or become CD25+Foxp3+ Treg 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 can develop among members of a cohort of autoreactive thymocytes that have evaded deletion by a self‐peptide, and that deletion and Treg formation can act together to bias the Treg repertoire toward low‐abundance self‐peptide(s).