Dynamic Changes in Chromatin Accessibility Occur in CD8 + T Cells Responding to Viral Infection

Immunity. 2016 Dec 20;45(6):1327-1340. doi: 10.1016/j.immuni.2016.10.028. Epub 2016 Dec 6.

Abstract

In response to acute infection, naive CD8+ T cells expand, differentiate into effector cells, and then contract to a long-lived pool of memory cells after pathogen clearance. During chronic infections or in tumors, CD8+ T cells acquire an "exhausted" phenotype. Here we present genome-wide comparisons of chromatin accessibility and gene expression from endogenous CD8+ T cells responding to acute and chronic viral infection using ATAC-seq and RNA-seq techniques. Acquisition of effector, memory, or exhausted phenotypes was associated with stable changes in chromatin accessibility away from the naive T cell state. Regions differentially accessible between functional subsets in vivo were enriched for binding sites of transcription factors known to regulate these subsets, including E2A, BATF, IRF4, T-bet, and TCF1. Exhaustion-specific accessible regions were enriched for consensus binding sites for NFAT and Nr4a family members, indicating that chronic stimulation confers a unique accessibility profile on exhausted cells.

Publication types

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

MeSH terms

  • Animals
  • Arenaviridae Infections / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Chromatin
  • Chromatin Assembly and Disassembly / immunology*
  • Disease Models, Animal
  • Gene Expression / immunology*
  • Gene Expression Profiling
  • Immunologic Memory / immunology*
  • Lymphocyte Activation / immunology*
  • Lymphocytic choriomeningitis virus
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic

Substances

  • Chromatin