The Function of NKT Cells During T Cruzi Infection

描述：(改编自申请者摘要)本项目的长期目标 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 慢性感染小鼠，是研究机制的极佳系统 感染引起的慢性炎症。 自然杀伤T(NKT)细胞似乎具有抑制 不想要的反应，但当感染发生时，他们可以通过 启动保护性反应。NKT细胞对 激活诱导细胞死亡，它们的重复刺激导致死亡或 改变Th细胞因子的产生。许多慢性炎症和自身免疫 疾病与NKT细胞数量减少或 改变Th细胞因子的产生。慢性刺激或慢性刺激的效果 对NKT细胞的感染尚不清楚。NKT细胞的候选抗原， 葡萄糖磷酸肌醇(GPI)是克氏锥虫大量表达的蛋白质。在T. 克鲁兹病毒感染后NKT细胞在保护性和慢性中的作用 炎症反应还没有被检查。此应用程序的特定目标 是为了确定在感染弓形虫期间NKT细胞在以下方面的功能： 保护性免疫反应；主要的MHCII、CD4、IFNy反应的调节； 以及慢性炎症反应。这些反应将在野外进行分析 型小鼠、NKT细胞缺陷小鼠和NKT细胞缺陷小鼠过继 用野生型NKT细胞或缺乏效应功能的NKT细胞转移 使用细胞免疫学和组织学技术。完成这些工作 AIMS将为NKT细胞在保护过程中的功能提供重要的见解 和病理性免疫反应。

DESCRIPTION: (Adapted from applicant's abstract) This project's long-term goals are to understand mechanisms of chronic inflammatory diseases. Infections initiate or perpetuate many chronic inflammatory diseases. Trypanosoma cruzi chronically infects mice and is an excellent system to investigate mechanisms of infection-induced chronic inflammation. Natural killer T (NKT) cells appear to function as sentinels that inhibit unwanted responses, but when infections occur they can rapidly respond by initiating protective responses. NKT cells are highly sensitive to activation-induced cell death, and their repeated stimulation leads to death or altered Th cytokine production. Many chronic inflammatory and autoimmune diseases are associated with NKT cell populations that are diminished or have altered Th cytokine production. The effect of chronic stimulation or chronic infection on NKT cells is unknown. A candidate antigen of NKT cells, glycophosphoinositol (GPI), is abundantly expressed by T. cruzi. During T. cruzi infection the function of NKT cells in the protective and chronic inflammatory responses have not been examined. This application's specific aims are to determine during T. cruzi infection the function of NKT cells in: the protective immune response; the regulation of a major MHCII CD4 IFNy response; and the chronic inflammatory response. These responses will be analyzed in wild type mice, NKT cell-deficient mice, and NKT cell-deficient mice adoptively transferred with wild type NKT cells or NKT cells lacking effector functions using cellular immunological and histological techniques. Completion of these aims will provide important insights into NKT cell functions during protective and pathologic immune responses.