Cytokines and transcription factors that regulate T helper cell differentiation: new players and new insights

J Clin Immunol. 2003 May;23(3):147-61. doi: 10.1023/a:1023381027062.


The differentiation of naive CD4+ T cells into subsets of T helper cells is a pivotal process with major implications for host defense and the pathogenesis of immune-mediated diseases. Though the basic paradigm was discovered more than 15 years ago, new discoveries continue to be made that offer fresh insights into the regulation of this process. T helper (TH)1 cells produce interferon (IFN)-gamma, promoting cell-mediated immunity and control of intracellular pathogens. We now know that TH1 differentiation is regulated by transcription factors such as T-bet, Stat1, and Stat4, as well as cytokines such as IL-12, IL-23, IL-27, type I IFNs, and IFN-gamma. In contrast, TH2 cells produce IL-4, which promotes allergic responses and is important in host defense against helminths. The transcription factors Stat6, GATA-3, c-Maf, NFATs, and the cytokine IL-4 promote TH2 differentiation. These key regulators of TH differentiation are the subject of this review.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cytokines / physiology*
  • Humans
  • Signal Transduction / immunology*
  • T-Lymphocytes, Helper-Inducer / cytology*
  • Transcription Factors / physiology*


  • Cytokines
  • Transcription Factors