Journal of Clinical Immunology

, Volume 23, Issue 3, pp 147–161 | Cite as

Cytokines and Transcription Factors That Regulate T Helper Cell Differentiation: New Players and New Insights

  • Davide Agnello
  • Carla S. R. Lankford
  • Jay Bream
  • Akio Morinobu
  • Massimo Gadina
  • John J. O'SheaEmail author
  • David M. Frucht


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 (1). T helper (TH)1 cells produce interferon (IFN)-γ, 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-γ. 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.

T helper (TH) cells differentiation TH1 cells TH2 cells interferon-γ interleukin (IL)-4 IL-12 IL-23 IL-27 Stat1 Stat4 Stat6 GATA-3 c-Maf NFATs 


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Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Davide Agnello
    • 1
  • Carla S. R. Lankford
    • 2
  • Jay Bream
    • 1
  • Akio Morinobu
    • 1
  • Massimo Gadina
    • 3
  • John J. O'Shea
    • 1
    Email author
  • David M. Frucht
    • 2
  1. 1.Molecular Immunology and Inflammation BranchNational Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Building 10, Room 9N262Bethesda
  2. 2.Division of Monoclonal AntibodiesCenter for Biologics Evaluation and Research, Food and Drug AdministrationBethesda
  3. 3.Department of Microbiology and ImmunologyQueen's UniversityBelfast, Northern IrelandUK

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