The Journal of Experimental Medicine
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Published 2 February 2004. doi:10.1084/jem.20031323
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 3, 423-428
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Brief Definitive Report

 GATA-3 in Human T Cell Helper Type 2 Development

Alla Skapenko1,2, Jan Leipe1,2, Uwe Niesner3, Koen Devriendt4, Rolf Beetz5, Andreas Radbruch3, Joachim R. Kalden2, Peter E. Lipsky6, and Hendrik Schulze-Koops1,2

1 Nikolaus Fiebiger Center for Molecular Medicine, Clinical Research Group III
2 Department of Internal Medicine III, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
3 Deutsches Rheuma-Forschungszentrum, 10117 Berlin, Germany
4 Department of Clinical Genetics, Centre for Human Genetics, University of Leuven, 3300 Leuven, Belgium
5 University Children's Hospital, 55101 Mainz, Germany
6 National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892

Address correspondence to Hendrik Schulze-Koops, Nikolaus Fiebiger Center for Molecular Medicine, Clinical Research Group III, University of Erlangen-Nuremberg, Glueckstrasse 6, 91054 Erlangen, Germany. Phone: 49-9131-853-3795; Fax: 49-9131-853-4770; email: Schulze-Koops{at}med3.imed.uni-erlangen.de

The delineation of the in vivo role of GATA-3 in human T cell differentiation is a critical step in the understanding of molecular mechanisms directing human immune responses. We examined T cell differentiation and T cell–mediated effector functions in individuals lacking one functional GATA-3 allele. CD4 T cells from GATA-3+/- individuals expressed significantly reduced levels of GATA-3, associated with markedly decreased T helper cell (Th)2 frequencies in vivo and in vitro. Moreover, Th2 cell–mediated effector functions, as assessed by serum levels of Th2-dependent immunoglobulins (Igs; IgG4, IgE), were dramatically decreased, whereas the Th1-dependent IgG1 was elevated compared with GATA-3+/+ controls. Concordant with these data, silencing of GATA-3 in GATA-3+/+ CD4 T cells with small interfering RNA significantly reduced Th2 cell differentiation. Moreover, GATA-3 mRNA levels increased under Th2-inducing conditions and decreased under Th1-inducing conditions. Taken together, the data strongly suggest that GATA-3 is an important transcription factor in regulating human Th2 cell differentiation in vivo.

Key Words: Th1/Th2 cells • cellular differentiation • transcription factors • T lymphocytes • siRNA

A. Skapenko and J. Leipe contributed equally to this work.


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