New Insights into Epigenetic Regulation of T Cell Differentiation

Immature CD4^- CD8^- thymocytes progress through several developmental steps in the thymus, ultimately emerging as mature CD4⁺ (helper) or CD8⁺ (cytotoxic) T cells. Activation of naïve CD4⁺ and CD8⁺ T cells in the presence of specific cytokines results in the induction of transcriptional programs that result in their differentiation into effector or memory cells and in the case of CD4⁺ T cells, the adoption of distinct T-helper fates. Previous studies have shown that histone modification and DNA methylation play important roles in each of these events. More recently, the roles of specific epigenetic regulators in T cell differentiation have been clarified. The identification of the epigenetic modifications and modifiers that control mature T cell differentiation and specification has also provided further insights into how dysregulation of these processes can lead to cancer or autoimmune diseases. In this review, we summarize recent findings that have provided new insights into epigenetic regulation of T cell differentiation in both mice and humans.