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. Author manuscript; available in PMC: 2021 Jan 1.
Published in final edited form as: Trends Immunol. 2019 Dec 4;41(1):17–28. doi: 10.1016/j.it.2019.11.004

Figure 2. Epigenetic regulation of CD8+ terminal effector (TE) and memory-precursors effector cell (MPEC) differentiation.

Figure 2.

Following activation by a professional APC, naïve CD8+ T cells undergo epigenetic reprogramming of genes related to stemness such as Tcf7 (TCF1) and Lef1, and tissue homing such as Sell (CD62L) and Il7R. These epigenetic changes include DNA methylation and demethylation events and an array of histone modifications. Inhibition of de novo DNA methylation or histone methylation restricts the progression of early effector cells into terminally differentiated T cells and/or increases the multipotency of MPECs. Deletion of Dnmt3a, a de novo methyltransferase, prior to effector differentiation has resulted in heightened re-expression of naïve-associated genes during the antigen-independent stage of memory CD8+ T cell differentiation in mice [67]. Genetic manipulation of H3K9me3 by Suv39h1 knockout (KO) in mice has resulted in increased expression of stem-like genes relative to wild type (WT) murine CD8+ T cells [66]. Likewise, manipulation of the polycomb repressive complex 2 (PRC2) has been demonstrated to promote increased skewing of cells towards an MPEC phenotype in mice following acute lymphocytic choriomeningitis virus (LCMV) infection [64]. However, conflicting reports of EZH2 on memory formation do exist [65]. Taken together, these studies highlight the role epigenetic programming plays in regulating the plasticity of CD8+ T cells during effector and memory differentiation.