Abstract
The process by which naïve CD8 T cells become activated, accumulate, and terminally differentiate as well as develop into memory cytotoxic T lymphocytes (CTLs) is central to the development of potent and durable immunity to intracellular infections and tumors. In this review, we discuss recent studies that have elucidated ancestries of short-lived and memory CTLs during infection, others that have shed light on gene expression programs manifest in individual responding cells and chromatin remodeling events, remodeling factors, and conventional DNA-binding transcription factors that stabilize the differentiated states after activation of naïve CD8 T cells. Several models have been proposed to conceptualize how naïve cells become memory CD8 T cells. A parsimonious solution is that initial naïve cell activation induces metastable gene expression in nascent CTLs, which act as progenitor cells that stochastically diverge along pathways that are self-reinforcing and result in shorter- versus longer-lived CTL progeny. Deciphering how regulatory factors establish and reinforce these pathways in CD8 T cells could potentially guide their use in immunotherapeutic contexts.
Highlights
During a prototypical acute intracellular infection that will be cleared, naïve antigen-specific CD8 T cells become activated and their progeny accumulates dramatically, a period generally referred to as the “effector” phase
Memory T cells are classically categorized into central memory T (Tcm) cells, which localize in secondary lymphoid organs (SLOs), and effector memory T (Tem) cells, which recirculate between peripheral tissues and SLOs4
At early memory time points, a substantial fraction of the classically defined Tem cells are more effector-like and have been termed effector-like memory cells or long-lived effector (LLE) cells[5,6]. Another subset of classic Tem cells, called peripheral memory T cells, has been delineated as those that recirculate through peripheral tissues via SLOs and has been distinguished from Tem cells that do not recirculate[7]
Summary
Faculty Reviews are review articles written by the prestigious Members of Faculty Opinions. The articles are commissioned and peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. 2. Peter N Cockerill , Institute of Biomedical Research, University of Birmingham, Birmingham, UK. Any comments on the article can be found at the end of the article
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