Role of the guanosine triphosphatase Rac2 in T helper 1 cell differentiation

Science. 2000 Jun 23;288(5474):2219-22. doi: 10.1126/science.288.5474.2219.

Abstract

T helper 1 (TH1) cells mediate cellular immunity, whereas TH2 cells potentiate antiparasite and humoral immunity. We used a complementary DNA subtraction method, representational display analysis, to show that the small guanosine triphosphatase Rac2 is expressed selectively in murine TH1 cells. Rac induces the interferon-gamma (IFN-gamma) promoter through cooperative activation of the nuclear factor kappa B and p38 mitogen-activated protein kinase pathways. Tetracycline-regulated transgenic mice expressing constitutively active Rac2 in T cells exhibited enhanced IFN-gamma production. Dominant-negative Rac inhibited IFN-gamma production in murine T cells. Moreover, T cells from Rac2-/- mice showed decreased IFN-gamma production under TH1 conditions in vitro. Thus, Rac2 activates TH1-specific signaling and IFN-gamma gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Gene Expression Regulation
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics*
  • JNK Mitogen-Activated Protein Kinases
  • Jurkat Cells
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic
  • RAC2 GTP-Binding Protein
  • Signal Transduction
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism*
  • Transfection
  • p38 Mitogen-Activated Protein Kinases
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*

Substances

  • Cytokines
  • NF-kappa B
  • Interferon-gamma
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • rac GTP-Binding Proteins