Stability and flexibility in chromatin structure and transcription underlies memory CD8 T-cell differentiation
Open Access
- 31 July 2019
- journal article
- review article
- Published by F1000 Research Ltd in F1000Research
- Vol. 8, 1278
- https://doi.org/10.12688/f1000research.18211.1
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.Keywords
Funding Information
- U.S. Department of Defense (W81XWH-16-1-0006)
- National Institutes of Health (R01AI095634, U19AI109976)
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