T. cruzi-induced Protective and Pathologic CD4 Responses

描述（由申请人提供）：本研究的长期目标 是了解慢性炎症性疾病的机制。感染 引发或延续许多慢性炎性疾病。克氏锥虫 小鼠感染是研究感染诱导的 慢性炎症在T.哺乳动物克氏感染CD 4 T细胞 反应是至关重要的控制寄生虫和产生慢性 炎症霸王CD 4反应的cruzi抗原是未知的 限制了进一步的调查。 霸王Cruzi转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 答案未知。在T. cruzi感染的表位，表位1， 转唾液酸酶超家族蛋白SA 85 - 1，似乎刺激了大的CD 4+细胞， 反应本项目研究这种反应在控制 寄生虫并导致随后的慢性炎症。细胞免疫学 分子生物学技术将用于开发表位1特异性T细胞， 细胞克隆和TCR转基因小鼠。在T.这些T细胞 将用于分析：SA 85 -1.1蛋白的大小和特异性， 表位1应答;表位1特异性T细胞克隆用于 保护，克隆的能力，造成慢性炎症;和天真的 表位1特异性CD 4 T细胞应答和这些细胞控制T. 并引起慢性炎症。这些目标的实现将澄清 T的关系。cruzi诱导的保护性和炎性T细胞应答， 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.