Zheng W, Flavell R A
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
Cell. 1997 May 16;89(4):587-96. doi: 10.1016/s0092-8674(00)80240-8.
CD4 T cells potentiate the inflammatory or humoral immune response through the action of Th1 and Th2 cells, respectively. The molecular basis of the differentiation of these cells from naive T cell precursors is, however, unclear. We found that GATA-3 was selectively expressed in Th2 cells. GATA-3 is expressed at a high level in naive, freshly activated T cells and Th2 lineage cells, but subsides to a minimal level in Th1 lineage cells as naive cells commit to their Th subset. Antisense GATA-3 inhibited the expression of all Th2 cytokine genes in the Th2 clone D10. GATA-3 directly activated an IL-4 promoter-luciferase reporter gene in M12 cells. In transgenic mice, elevated GATA-3 in CD4 T cells caused Th2 cytokine gene expression in developing Th1 cells. Thus, GATA-3 is necessary and sufficient for Th2 cytokine gene expression.
CD4 T细胞分别通过Th1细胞和Th2细胞的作用增强炎症或体液免疫反应。然而，这些细胞从初始T细胞前体分化的分子基础尚不清楚。我们发现GATA-3在Th2细胞中选择性表达。GATA-3在初始的、刚激活的T细胞和Th2谱系细胞中高水平表达，但随着初始细胞分化为Th亚群，其在Th1谱系细胞中的表达降至最低水平。反义GATA-3抑制了Th2克隆D10中所有Th2细胞因子基因的表达。GATA-3在M12细胞中直接激活了IL-4启动子-荧光素酶报告基因。在转基因小鼠中，CD4 T细胞中GATA-3水平升高导致发育中的Th1细胞表达Th2细胞因子基因。因此，GATA-3对于Th2细胞因子基因表达是必需且充分的。
