An epigenetic view of helper T cell differentiation

Nat Immunol. 2003 Jul;4(7):616-23. doi: 10.1038/ni0703-616.


Antigen and cytokine receptor signals act in synergy to direct the differentiation of CD4+ T cells. These signals initiate reciprocal activation and silencing of the interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) cytokine gene loci, changes that are heritably maintained in the resulting T helper type 1 (T(H)1) or T(H)2 cells and their progeny. Early, unpolarized transcription and chromatin remodeling of the poised cytokine genes of naive T cells is followed by consolidation and spreading of epigenetic changes and the establishment of self-reinforcing transcription factor networks. Recent studies have begun to elucidate the molecular mechanisms that establish and maintain polarized cytokine gene expression, and thus the cellular identity of differentiated helper T cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Chromatin / physiology
  • Chromosome Mapping
  • DNA-Binding Proteins / physiology
  • GATA3 Transcription Factor
  • Gene Expression Regulation
  • Gene Silencing
  • Humans
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics*
  • Promoter Regions, Genetic
  • T-Lymphocytes, Helper-Inducer / physiology*
  • Trans-Activators / physiology
  • Transcription, Genetic


  • Chromatin
  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Trans-Activators
  • Interleukin-4