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Science 288 (5474): 2219-2222

Copyright © 2000 by the American Association for the Advancement of Science

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

Baiyong Li, 12*dagger Hong Yu, 12dagger Wei-ping Zheng, 1ddagger Reinhard Voll, 12§ Songqing Na, 1parallel Andrew W. Roberts, 3 David A. Williams, 3 Roger J. Davis, 4 Sankar Ghosh, 125 Richard A. Flavell 12#

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.

1 Section of Immunobiology and
2 Howard Hughes Medical Institute, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06520-8011, USA.
3 Section of Pediatric Hematology/Oncology, Wells Center for Pediatric Research, Howard Hughes Medical Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
4 Howard Hughes Medical Institute, University of Massachusetts Medical Center, Worcester, MA 01605, USA.
5 Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8024, USA.
*   Present address: Pfizer, Groton, CT 06340, USA.

dagger    These authors contributed equally to this work.

ddagger    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.

parallel    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}yale.edu

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