Ho I C, Lo D, Glimcher L H
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
J Exp Med. 1998 Nov 16;188(10):1859-66. doi: 10.1084/jem.188.10.1859.
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.
c-maf原癌基因是一种2型辅助性T细胞（Th2）特异性转录因子，在体外可激活白细胞介素（IL）-4启动子。尽管据推测c-maf在体内指导IL-4基因的Th2特异性表达，但缺乏c-maf在正常原代T细胞分化过程中发挥作用的直接证据。我们现在证明，体内c-maf的过表达使Th免疫反应偏向Th2途径，这表现为Th2细胞因子以及IL-4依赖性免疫球蛋白IgG1和IgE的产生增加。CD4启动子/c-maf转基因小鼠中IgG1和IgE的过量产生依赖于IL-4，因为在培育到IL-4缺陷背景的c-maf转基因小鼠中未观察到这种情况。c-maf在成熟Th1细胞中的异位表达并未赋予它们产生IL-4的能力，但确实降低了IFN-γ的产生。c-maf过表达对Th1分化的减弱是通过一种独立于IL-4和其他Th2细胞因子的机制发生的，并且可以被IL-12克服。这些研究表明，c-maf通过IL-4依赖性机制促进Th2分化，并通过Th2细胞因子非依赖性机制减弱Th1分化。
