IL-4 INDEPENDENT IL-13 MEDIATED PROTECTIVE IMMUNITY

鞭虫属的胃肠道线虫引起巨大的 发病率和增加对人类感染因子的易感性。免疫 已经证明对鞭虫感染的保护是T细胞依赖性的 并与IgE升高和肥大细胞增多症有关。我们利用自然的 鼠寄生虫，毛首线虫，作为一个模型，了解发展 的保护性反应。在我们的研究中，我们最近发现了一种 新奇的途径，导致蠕虫驱逐这种寄生虫。封闭性T细胞 与B7拮抗剂CTLA 4 Ig共刺激，触发免疫偏离， 以IL-4升高为特征的宿主保护性2型免疫应答 和IL-13升高。IFN-γ的额外阻断恢复了宿主的保护性 反应，虽然IL-4水平仍然受到抑制。进一步的研究表明， IFN-γ阻断后可能发生的IL-4非依赖性保护性反应是 IL-13依赖性，表明IL-13可以介导宿主保护作用。 缺乏2型IL-4显性免疫应答。在这些研究中，我们建议 分析IL-13表达和功能在B7 封锁T.小鼠粘膜体内免疫应答， 以下具体目的：1）鉴定产生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 在IFN-γ显性应答期间导致IL-13产生的途径; 3） 确定IFN-γ调节IL-13效应子功能的机制。

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.