Central CD4 ⁺ T cell tolerance: deletion versus regulatory T cell differentiation

The diversion of MHC class II-restricted thymocytes into the regulatory T (T _reg ) cell lineage is driven by intrathymic encounter of agonist self-antigens in a similar manner to the clonal deletion of thymocytes. Somewhat paradoxically, it thus seems that the expression of an autoreactive T cell receptor is a shared characteristic of T cells that are subject to clonal deletion and T cells that are diverted into the T _reg cell lineage. Here, we discuss how thymocyte-intrinsic and thymocyte-extrinsic determinants may specify the choice between these two fundamentally different T cell fates.