The transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses

Immunity. 2012 Oct 19;37(4):660-73. doi: 10.1016/j.immuni.2012.09.007. Epub 2012 Oct 4.


T-bet is a critical transcription factor for T helper 1 (Th1) cell differentiation. To study the regulation and functions of T-bet, we developed a T-bet-ZsGreen reporter mouse strain. We determined that interleukin-12 (IL-12) and interferon-γ (IFN-γ) were redundant in inducing T-bet in mice infected with Toxoplasma gondii and that T-bet did not contribute to its own expression when induced by IL-12 and IFN-γ. By contrast, T-bet and the transcription factor Stat4 were critical for IFN-γ production whereas IFN-γ signaling was dispensable for inducing IFN-γ. Loss of T-bet resulted in activation of an endogenous program driving Th2 cell differentiation in cells expressing T-bet-ZsGreen. Genome-wide analyses indicated that T-bet directly induced many Th1 cell-related genes but indirectly suppressed Th2 cell-related genes. Our study revealed redundancy and synergy among several Th1 cell-inducing pathways in regulating the expression of T-bet and IFN-γ, and a critical role of T-bet in suppressing an endogenous Th2 cell-associated program.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Differentiation
  • GATA3 Transcription Factor / immunology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-4 / immunology
  • Mice
  • Mice, Knockout
  • STAT4 Transcription Factor / deficiency
  • STAT4 Transcription Factor / immunology
  • Signal Transduction*
  • T-Box Domain Proteins / deficiency
  • T-Box Domain Proteins / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Toxoplasma / immunology
  • Toxoplasmosis / immunology


  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • STAT4 Transcription Factor
  • Stat4 protein, mouse
  • T-Box Domain Proteins
  • Interleukin-4
  • Interferon-gamma

Associated data

  • GEO/GSE38808