Kaplan M H, Grusby M J
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
J Leukoc Biol. 1998 Jul;64(1):2-5. doi: 10.1002/jlb.64.1.2.
It is now well appreciated that the cytokines interleukin (IL)-12 and IL-4 are important for the generation of Th1 and Th2 cells, respectively. Only recently, however, have the molecular mechanisms by which these cytokines affect Th cell differentiation begun to be defined. Previous work from our laboratory has demonstrated that members of the signal transducer and activator of transcription (STAT) gene family are critical for the differentiation of Th cell subsets. In particular, Stat4-deficient mice show an impairment in the generation of Th1 cells, whereas Stat6-deficient animals do not generate Th2 cells. We have now generated Stat4-Stat6 double-deficient mice to determine whether STAT-independent pathways exist for the development of Th cell subsets. It is surprising that Th1 but not Th2 cells can be generated from double-deficient mice in vitro and these animals are able to mount an in vivo Th1 cell-mediated immune response. These results suggest a model of Th cell differentiation in which Stat4 and Stat6 have different roles in the development of Th cell subsets.
现在人们已经充分认识到，细胞因子白细胞介素（IL）-12和IL-4分别对Th1和Th2细胞的生成很重要。然而，直到最近，这些细胞因子影响Th细胞分化的分子机制才开始得到明确。我们实验室之前的工作表明，信号转导和转录激活因子（STAT）基因家族成员对Th细胞亚群的分化至关重要。特别是，Stat4缺陷小鼠在Th1细胞生成方面存在缺陷，而Stat6缺陷动物则不产生Th2细胞。我们现在已经培育出Stat4-Stat6双缺陷小鼠，以确定Th细胞亚群的发育是否存在不依赖STAT的途径。令人惊讶的是，在体外双缺陷小鼠能够产生Th1细胞而不是Th2细胞，并且这些动物能够在体内引发Th1细胞介导的免疫反应。这些结果提示了一种Th细胞分化模型，其中Stat4和Stat6在Th细胞亚群的发育中具有不同的作用。
