Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism

Immunity. 1998 Nov;9(5):745-55. doi: 10.1016/s1074-7613(00)80671-8.


Recently, the transcription factor GATA-3 was shown to be selectively expressed in Th2 but not Th1 cells and to augment Th2-specific cytokines. Here, we show that loss of GATA-3 expression by developing Th1 cells requires IL-12 signaling through Stat4 and does not simply result from an absence of IL-4. Moreover, we demonstrate a novel role for GATA-3 in directly repressing Th1 development distinct from its positive actions on Th2-specific cytokines. GATA-3 inhibits Th1 cytokines by a cell-intrinsic mechanism that is not dependent on IL-4 and that may involve repression of IL-12 signaling. Thus, GATA-3 expression and IL-12 signaling are mutually antagonistic, which facilitates rapid dominance of one pathway during early Th development, producing a stable divergence in cytokine profiles.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • DNA-Binding Proteins / physiology*
  • GATA3 Transcription Factor
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / physiology
  • Interleukin-4 / physiology*
  • Mice
  • Mice, Transgenic
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • Signal Transduction / physiology
  • Th1 Cells / cytology*
  • Th1 Cells / physiology
  • Trans-Activators / physiology*


  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Gata3 protein, mouse
  • Interleukin-2
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • Stat4 protein, mouse
  • Trans-Activators
  • Interleukin-4
  • Interferon-gamma