查看文章

Activation of naïve CD4+ T cells by T cell receptor (TCR) stimulation and cytokine cues lead to differentiation into effector T cell populations with distinct pro-inflammatory or regulatory functions. Unlike adult naïve T cells, human fetal naïve CD4+ T cells uniquely differentiate into FOXP3+ regulatory T (T reg) cells upon TCR activation independent of exogenous cytokine signalling. This facility for T reg differentiation is crucial for generating tolerance in utero; however, the mechanisms underlying this ability in fetal naïve cells are largely unknown. Here, we reveal FOXP3-independent transcriptional and epigenetic programs shared between fetal naive T cells and committed adult T reg cells that are inactive in adult naive T cells. We show that a subset of adult T reg-specific super-enhancers is active within fetal naive T cells, including two super-enhancers at Helios, a thymic T reg gene. Helios is expressed in fetal naive …