Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses.
Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses.
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DOI：
10.1084/jem.189.10.1565
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发表时间：
1999-05-17
期刊：
影响因子：
--
通讯作者：
McKenzie AN
中科院分区：
文献类型：
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作者：
McKenzie GJ;Fallon PG;Emson CL;Grencis RK;McKenzie AN
使用单一载体靶向策略，我们已经产生了白细胞介素（IL）-4和IL-13的联合缺乏症的小鼠，以阐明其在辅助性T细胞2型（Th 2）细胞应答中的作用。使用免疫挑战通常特征在于Th 2样反应，我们已经比较了双缺陷小鼠与野生型，IL-4缺陷，IL-13缺陷小鼠产生的反应。使用肺肉芽肿模型，诱导与曼氏血吸虫卵，我们证明，虽然嗜酸性粒细胞浸润，免疫球蛋白E，和IL-5的生产减少在IL-4-缺陷型小鼠和IL-13-缺陷型小鼠，他们被取消只有在这两种细胞因子的组合情况下。此外，IL-4/13缺乏的动物在其排出胃肠道线虫巴西日本圆线虫的能力方面严重受损。出乎意料的是，N。巴西脑炎病毒感染的IL-4/13缺陷小鼠出现IL-5和嗜酸性粒细胞增多，表明存在IL-5表达的代偿机制，尽管血清IgE仍然检测不到。IL-4/13缺陷型小鼠默认为Th 1样表型，其特征在于干扰素γ的表达和IgG 2a和IgG 2b的产生。我们的结论是，IL-4和IL-13合作启动快速Th 2细胞驱动的反应，虽然他们的功能重叠，他们执行添加剂的作用。
Using a single vector targeting strategy, we have generated mice with a combined deficiency of interleukin (IL)-4 and IL-13 to clarify their roles in T helper type 2 (Th2) cell responses. Using immunological challenges normally characterized by a Th2-like response, we have compared the responses of the double-deficient mice with those generated by wild-type, IL-4–deficient, and IL-13–deficient mice. Using a pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that although eosinophil infiltration, immunoglobulin E, and IL-5 production are reduced in the IL-4–deficient mice and IL-13–deficient mice, they are abolished only in the combined absence of both cytokines. Furthermore, IL-4/13–deficient animals are severely impaired in their ability to expel the gastrointestinal nematode Nippostrongylus brasiliensis. Unexpectedly, N. brasiliensis–infected IL-4/13–deficient mice developed elevated IL-5 and eosinophilia, indicating that compensatory mechanisms exist for the expression of IL-5, although serum IgE remained undetectable. IL-4/13–deficient mice default to a Th1-like phenotype characterized by the expression of interferon γ and the production of IgG2a and IgG2b. We conclude that IL-4 and IL-13 cooperate to initiate rapid Th2 cell–driven responses, and that although their functions overlap, they perform additive roles.