T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cells

Nat Immunol. 2002 Jun;3(6):549-57. doi: 10.1038/ni794. Epub 2002 May 13.


T helper type 1 (T(H)1) cell development involves interferon-gamma (IFN-gamma) signaling through signal transducer and activator of transcription 1 (STAT1) and interleukin-12 (IL-12) signaling through STAT4 activation. We examined here T-bet regulation and evaluated the actions of T-bet in STAT1- and STAT4-dependent T(H)1 development processes. We found that T-bet expression during T cell activation was strongly dependent on IFN-gamma signaling and STAT1 activation, but was independent of STAT4. Ectopic T-bet expression strongly increased IFN-gamma production in T(H)2 cells activated by PMA-ionomycin, but weakly increased IFN-gamma production in T(H)2 cells stimulated by IL-12 IL-18 or OVA peptide antigen-presenting cell stimulation. In contrast, IL-12 IL-18 induced IFN-gamma production remained STAT4-dependent despite ectopic T-bet expression. Ectopic T-bet expression selectively induced expression of IL-12Rbeta2, but not IL-18Ralpha, in wild-type and STAT1(-/-) T(H)2 cells, but did not extinguish expression of GATA-3 and T(H)2 cytokines. Finally, ectopic T-bet did not directly induce expression of endogenous T- bet independently of IFN-gamma or STAT1. Thus, T-bet is induced by IFN-gamma and STAT1 signaling during T cell activation. In addition, T-bet mediates STAT1-dependent processes of T(H)1 development, including the induction of IL-12Rbeta2.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Differentiation
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Interferon-gamma / metabolism
  • Interleukin-12 / pharmacology
  • Interleukin-18 / pharmacology
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-12
  • STAT1 Transcription Factor
  • STAT4 Transcription Factor
  • Signal Transduction
  • T-Box Domain Proteins
  • Th2 Cells / cytology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Interleukin-18
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • STAT1 Transcription Factor
  • STAT4 Transcription Factor
  • Stat1 protein, mouse
  • Stat4 protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Trans-Activators
  • Transcription Factors
  • Interleukin-12
  • Interferon-gamma