An alternate pathway for type 1 T cell differentiation
An alternate pathway for type 1 T cell differentiation
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DOI：
10.1093/intimm/11.8.1185
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发表时间：
1999-08-01
影响因子：
4.4
通讯作者：
Asano, Y
中科院分区：
文献类型：
--
作者：
Feng, CG;Watanabe, S;Asano, Y
IFN-调节因子-1（IRF-1）基因破坏小鼠在IL-12和IL-18基因表达分别在转录和翻译后水平上存在缺陷。由于IL-12 p40基因的诱导受损，突变小鼠在细菌感染后产生2型T细胞应答，而产生IFN-γ的1型T细胞未被诱导。然而，我们在这里发现，不同的病原体激活了一种新的途径，即使在IRF-1缺陷小鼠中也能诱导产生IFN-γ的1型T细胞。该途径不依赖于IL-12和IL-18，并且由巨噬细胞谱系细胞的不同功能介导。突变小鼠的巨噬细胞不能激活IL-12依赖性途径，但它们在疟原虫感染小鼠中的IL-12非依赖性途径中起作用。这导致了诱导产生IFN-γ的T细胞的IL-12非依赖性新途径与经典的1型/2型T细胞亚群分化途径不同的假设。
IFN-regulatory factor-1 (IRF-1) gene-disrupted mice are defective in IL-12 and IL-18 gene expression at the transcriptional and post-translational level respectively, The mutant mouse mounts a type 2 T cell response upon bacterial infection because of the impaired induction of the IL-12 p40 gene and IFN-gamma-producing type 1 T cells are not induced. We showed here, however, that different pathogens activate a novel pathway for inducing IFN-gamma-producing type 1 T cells even in an IRF-1-deficient mouse. This pathway is independent of IL-12 and IL-18, and is mediated by a distinct function of macrophage lineage cells. Macrophages of the mutant mice fail to activate the IL-12-dependent pathway, but they function in the IL-12-independent pathway in Plasmodium-infected mice. This leads to the hypothesis that the IL-12-independent novel pathway for inducing IFN-gamma-producing T cells is distinct from the classical type 1/type 2 T cell subset differentiation pathway.