Thymically imprinted heterogeneity results in differential Treg induction and stability of effector identity.

Thymic selection predisposes naive T cells to particular outcomes when challenged later with cognate antigen, whether the antigen is self or foreign. This suggests that there is an inherent heterogeneity of functioning among T cells within the naive population (both CD4 and CD8), and that each T cell, as part of its thymic development, is given a certain "programming" that will affect its eventual fate decisions. In this project, we looked at the primary effects of this thymic imprinting on the conversion of naive CD4 T cells into Tregs. Furthermore, using an induced-Treg-reporter system, we examine the impact of thymic imprinted heterogeneity on effector functionality and identity stability. We report that naive T cell differential responsivity to cytokines leads to the observed difference in Treg induction and that the Tregs induced from T cells of different self-affinities maintain a heterogeneity of effector function and identity.