The Transcription Factor GATA-3 Is Necessary and Sufficient for Th2 Cytokine Gene Expression in CD4 T Cells

Cell. 1997 May 16;89(4):587-96. doi: 10.1016/s0092-8674(00)80240-8.

Abstract

CD4 T cells potentiate the inflammatory or humoral immune response through the action of Th1 and Th2 cells, respectively. The molecular basis of the differentiation of these cells from naive T cell precursors is, however, unclear. We found that GATA-3 was selectively expressed in Th2 cells. GATA-3 is expressed at a high level in naive, freshly activated T cells and Th2 lineage cells, but subsides to a minimal level in Th1 lineage cells as naive cells commit to their Th subset. Antisense GATA-3 inhibited the expression of all Th2 cytokine genes in the Th2 clone D10. GATA-3 directly activated an IL-4 promoter-luciferase reporter gene in M12 cells. In transgenic mice, elevated GATA-3 in CD4 T cells caused Th2 cytokine gene expression in developing Th1 cells. Thus, GATA-3 is necessary and sufficient for Th2 cytokine gene expression.

MeSH terms

  • Animals
  • Base Sequence
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Division
  • Cytokines / genetics*
  • DNA Primers / genetics
  • DNA, Antisense / genetics
  • DNA, Antisense / pharmacology
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • GATA3 Transcription Factor
  • Gene Expression
  • In Vitro Techniques
  • Interleukin-4 / genetics
  • Kinetics
  • Mice
  • Mice, Transgenic
  • Phenotype
  • Promoter Regions, Genetic
  • Receptors, Antigen, T-Cell / metabolism
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transfection

Substances

  • Cytokines
  • DNA Primers
  • DNA, Antisense
  • DNA, Complementary
  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Receptors, Antigen, T-Cell
  • Trans-Activators
  • Interleukin-4