IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice
IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice
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DOI：
10.1038/ni725
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发表时间：
2001-11-01
影响因子：
30.5
通讯作者：
Röcken, M
中科院分区：
文献类型：
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作者：
Biedermann, T;Zimmermann, S;Röcken, M
对细胞内病原体感染的免疫受白细胞介素12 （IL-12）和白细胞介素4 （IL-4）的调节，IL-12介导保护性T辅助型I （T(H)1）反应，IL-4诱导T(H)2细胞和易感性。矛盾的是，我们在这里表明，当感染因子在树突状细胞（dc）的初始激活期间存在时，IL-4指示dc产生IL-12并促进T(H)1的发育。这种T(H)1反应在BALB/c易感小鼠中建立了对利什曼原虫的耐药性。随后，在T细胞启动期间，IL-4诱导T(H)2分化并在耐药小鼠中进展利什曼病。由于免疫应答是通过DC和T细胞的连续激活而形成的，因此IL-4对DC发育和T细胞分化的不同影响导致了具有相反功能表型的免疫应答。
Immunity to infection with intracellular pathogens is regulated by interleukin 12 (IL-12), which mediates protective T helper type I (T(H)1) responses, or IL-4, which induces T(H)2 cells and susceptibility. Paradoxically, we show here that when present during the initial activation of dendritic cells (DCs) by infectious agents, IL-4 instructed DCs to produce IL-12 and promote T(H)1 development. This T(H)1 response established resistance to Leishmania major in susceptible BALB/c mice. When present later, during the period of T cell priming, IL-4 induced T(H)2 differentiation and progressive leishmaniasis in resistant mice. Because immune responses developed via the consecutive activation of DCs and then T cells, the contrasting effects of IL-4 on DC development and T cell differentiation led to immune responses that had opposing functional phenotypes.