Role of the Guanosine Triphosphatase Rac2 in T Helper 1 Cell Differentiation

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Science  23 Jun 2000:
Vol. 288, Issue 5474, pp. 2219-2222
DOI: 10.1126/science.288.5474.2219

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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-γ (IFN-γ) 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-γ production. Dominant-negative Rac inhibited IFN-γ production in murine T cells. Moreover, T cells from Rac2−/− mice showed decreased IFN-γ production under TH1 conditions in vitro. Thus, Rac2 activates TH1-specific signaling and IFN-γ gene expression.

  • * Present address: Pfizer, Groton, CT 06340, USA.

  • These authors contributed equally to this work.

  • Present address: University of Rochester, Center for Vaccine Biology and Immunology, Post Office Box 609, Rochester, NY 14623, USA.

  • § Present address: Medizinische Klinik III, Immunologie Labor, Gluckstrabe 41, 91054 Erlangen, Germany.

  • || Present address: Lilly Research Laboratory, Eli Lilly and Company, Indianapolis, IN 46285, USA.

  • Present address: The Walter Eliza Hall Institute, Melbourne, Australia.

  • # To whom correspondence should be addressed: E-mail: fran.manzo{at}

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