J. Exp. Med., Volume 188, Number 10, November 16, 1998 1859-1866

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

By I-Cheng Ho,^* David Lo,^§ and Laurie H. Glimcher^*

From the ^* Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115; the  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-. 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.

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