Epigenetic priming as a driver of memory recall and dysfunction in T cells

T cells are essential for protective immunity against pathogens and malignancies. While the initial activation of a naive T cell is slow, antigen-experienced or memory T cells mount near-immediate protective responses through their remarkable capacity to instantaneously reactivate inflammatory gene programs upon antigen rechallenge. Evidence is emerging that this immunological memory is underpinned by dynamic changes at the chromatin level or epigenome of T cells. Here, we review recent findings on how epigenetic mechanisms are a driving force guiding initial T cell activation and differentiation, and durably endow memory T cells with the ability to remember gene regulatory processes essential for high-magnitude protective immune responses. We discuss the molecular programs that may be involved in the establishment and maintenance of chromatin-based information in memory T cells during homeostasis, and how undesired epigenetic priming may program T cells for dysfunction in patients with chronic immune-related disease and cancer.