IL-4 INDEPENDENT IL-13 MEDIATED PROTECTIVE IMMUNITY

鞭虫属的胃肠道线虫引起极大的 人类的发病率和对感染剂的易感性增加。免疫 对旋毛虫感染的保护已被证明是依赖T细胞的 并与IgE升高和肥大细胞增多症相关。我们使用了天然的 小鼠寄生虫Trichuris Muris作为了解发育的模型 是保护性反应的结果。在我们的研究中，我们最近发现了一种 这种寄生虫中的新奇途径导致了蠕虫的驱逐。阻断T细胞 协同刺激，与B7拮抗剂CTLA4lg，触发免疫偏离 以IL-4升高为特征的宿主保护性2型免疫反应 IL-13水平升高。额外阻断干扰素-γ可恢复宿主的保护作用 反应，尽管IL-4水平仍然受到抑制。进一步的研究表明， 干扰素-γ阻断后可发生的IL-4非依赖性保护性反应是 IL-13依赖，提示IL-13可介导宿主保护。 缺乏2型IL-4显性免疫反应。在这些研究中，我们提出 分析B7对IL-13表达和功能的调节作用 阻断小鼠毛滴虫黏膜体内免疫反应 以下具体目标：1)确定在以下情况下产生IL-13的细胞谱系 B7相互作用和IL-4的产生被阻断；2)检查分化 干扰素-γ显性反应中产生IL-13的途径； 确定干扰素-γ调节IL-13效应器功能的机制。

Gastrointestinal nematodes of the genus Trichuris cause great morbidity and increased susceptibility to infectious agents in humans. Immune protection against Trichuris infection has been shown to be T cell-dependent and associated with IgE elevations and mastocytosis. We have used the natural murine parasite, Trichuris muris, as a model for understanding the development of the protective response. In our studies, we have recently identified a novelty pathway leading to worm expulsion in this parasite. Blocking T cell costimulation, with the B7 antagonist, CTLA4lg, triggers immune deviation from a host protective type 2 immune response characterized by elevations in IL-4 and IL-13 elevations. Additional blockade of IFN-gamma restores the host protective response, although IL-4 levels remain inhibited. Further studies show that the IL-4 independent protective response that can occur following IFN-gamma blockade is IL-13 dependent, suggesting that IL-13 can mediate host protection in the absence of a type 2 IL-4 dominant immune response. In these studies, we propose to analyze the regulation of IL-13 expression and function following B7 blockade of the T. muris mucosal in vivo immune response addressing the following specific aims: 1) identify the cell lineage that produces IL-13 when B7 interactions and IL-4 production are blocked; 2) examine the differentiation pathway leading to IL-13 production during the IFN-gamma dominant response; 3) determine the mechanism of IFN-gamma modulation of IL-13 effector function.