T. cruzi-induced Protective and Pathologic CD4 Responses

描述(申请人提供)：本研究的长期目标 是为了了解慢性炎症性疾病的发病机制。感染 引发或延续许多慢性炎症性疾病。克氏锥虫 小鼠感染是研究感染诱导的一个很好的系统。 慢性炎症。哺乳动物感染克氏毛滴虫过程中的CD4T细胞 反应对控制寄生虫和产生慢性 发炎。Cd4反应中的克氏锥虫抗原尚不清楚。 限制了进一步的调查。 克鲁兹毛滴虫反式唾液酸酶超家族同时表达一个大的 变异表位的数量。这些变异表位对T细胞的影响 响应未知。在感染克氏锥虫期间，克氏原虫的表位1 反式唾液酸酶超家族蛋白SA85-1，似乎能刺激大量的CD4 回应。本项目调查了这种反应在控制中的作用 寄生虫并引起随之而来的慢性炎症。细胞免疫学 分子生物学技术将被用来开发表位1特异性T细胞 细胞克隆和TCR转基因小鼠。在感染克氏锥虫期间，这些T细胞 将用于分析：SA85-1.1蛋白的大小和特异性以及 表位1的反应；表位1特异性T细胞克隆用于 保护，以及克隆人引起慢性炎症的能力；以及天真的 表位1特异性的CD4T细胞应答和这些细胞控制T. 并引起慢性炎症。完成这些目标将澄清 克氏锥虫诱导的保护性和炎症性T细胞反应的关系， 并将提供对感染诱导的T细胞反应和慢性 炎症性疾病。

DESCRIPTION (provided by applicant): The long-term objectives of this research are to understand the mechanisms of chronic inflammatory diseases. Infections initiate or perpetuate many chronic inflammatory diseases. Trypanosoma cruzi infection of mice is an excellent system to investigate infection-induced chronic inflammation. During T. cruzi infection of mammals the CD4 T cell response is critical in controlling the parasite and in generating the chronic inflammation. The T. cruzi antigens of the CD4 response have been unknown limiting further investigations. The T. cruzi trans-sialidase superfamily simultaneously expresses a large number of variant epitopes. The effect of these variant epitopes on the T cell response is unknown. During T. cruzi infection an epitope, epitope 1, of the trans-sialidase superfamily protein SA85-.1, appears to stimulate a large CD4 response. This project investigates this response's contribution in controlling the parasite and causing the ensuing chronic inflammation. Cellular immunology and molecular biology techniques will be used to develop epitope 1- specific T cell clones and TCR transgenic mice. During T. cruzi infection, these T cells will be used to analyze: the size and specificity of the SA85-1.1 protein and epitope 1 responses; the mechanisms used by epitope 1 specific T cell clones to protect, and the clones' ability to cause chronic inflammation; and the naive epitope 1 specific CD4 T cell response and these cells' ability to control T. cruzi and cause chronic inflammation. Completion of these aims will clarify the relationship of T. cruzi-induced protective and inflammatory T cell responses, and will provide insight into infection-induced T cell responses and chronic inflammatory diseases.