The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1998/11/1859/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 10, November 16, 1998 1859-1866

Articles

c-maf Promotes T Helper Cell Type 2 (Th2) and Attenuates Th1 Differentiation by Both Interleukin 4–dependent and –independent Mechanisms

I-Cheng Ho*,{ddagger}, David Lo§, and Laurie H. Glimcher*,{ddagger}

From the * Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115; the {ddagger} Department of Immunology and Rheumatology, Harvard Medical School, Boston, Massachusetts 02115; and the § Department of Immunology, Scripps Research Institute, La Jolla, California 92037

The c-maf protooncogene is a T helper cell type 2 (Th2)-specific transcription factor that activates the interleukin (IL)-4 promoter in vitro. Although it has been postulated that c-maf directs the Th2-specific expression of the IL-4 gene in vivo, direct evidence that c-maf functions during the differentiation of normal, primary T cells is lacking. We now demonstrate that overexpression of c-maf in vivo skews the Th immune response along a Th2 pathway, as evidenced by increased production of Th2 cytokines and the IL-4–dependent immunoglobulins, IgG1 and IgE. The overproduction of IgGl and IgE in the CD4 promoter/c-maf transgenic mice was IL-4 dependent since this was not observed in c-maf transgenic mice bred onto an IL-4–deficient background. Ectopic expression of c-maf in mature Th1 cells did not confer on them the ability to produce IL-4, but did decrease the production of IFN-{gamma}. The attenuation of Th1 differentiation by c-maf overexpression occurred by a mechanism that was independent of IL-4 and other Th2 cytokines, and could be overcome by IL-12. These studies demonstrate that c-maf promotes Th2 differentiation by IL-4–dependent mechanisms and attenuates Th1 differentiation by Th2 cytokine-independent mechanisms.

Key Words: interleukin 4 • T helper cells • c-maf • transcription factor

Address correspondence to Laurie H. Glimcher, Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Ave., FXB-2, Boston, MA 02115-6017. Phone: 617-432-0622; Fax: 617-432-0084; E-mail: lglimche{at}hsph.harvard.edu

Abbreviations used: NFAT, nuclear factor of activated T cells; RT, reverse transcription.


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