Stability and flexibility in chromatin structure and transcription underlies memory CD8 T-cell differentiation

F1000Res. 2019 Jul 31:8:F1000 Faculty Rev-1278. doi: 10.12688/f1000research.18211.1. eCollection 2019.

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: Memory CD8 T cells; chromatin structure; transcriptional control.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • CD8-Positive T-Lymphocytes / cytology*
  • Cell Differentiation*
  • Chromatin / chemistry*
  • Humans
  • Immunologic Memory
  • Lymphocyte Activation

Substances

  • Chromatin