Thymically imprinted differential responsivity of naïve CD4 T cells to IL2 results in a heterogeneity of both Treg induction and subsequent effector functioning

Abstract

ABSTRACTThymic 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 CD8s), and that each T cell, as part of its thymic development, is given a certain ‘programming’ which will affect its eventual fate decisions. In this project, we looked at the primary effects of this thymic imprinting on the conversion of naïve CD4 T cells into Tregs. Further, using an induced-Treg-reporter system, we exam the impact of thymic imprinted heterogeneity on effector functionality and identity stability. We report that naïve 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.