The Function of NKT Cells During T Cruzi Infection

描述：（改编自申请人的摘要）本项目的长期目标 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 慢性感染小鼠，是研究机制的极好系统 感染引起的慢性炎症 自然杀伤T（NKT）细胞似乎起着哨兵的作用， 不必要的反应，但当感染发生时，他们可以迅速作出反应， 启动保护性反应。NKT细胞对 激活诱导的细胞死亡，并且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性 疾病与NKT细胞群减少或 改变Th细胞因子的产生。慢性刺激或慢性 对NKT细胞的感染是未知的。NKT细胞的候选抗原， 糖磷酸肌醇（GPI）在T.克鲁兹在T. Cruzi感染后NKT细胞在保护性和慢性 炎症反应尚未被检测。该应用程序的具体目标 在T. Cruzi感染NKT细胞的功能： 保护性免疫应答;主要MHCII CD 4 IFN γ应答的调节; 和慢性炎症反应。这些反应将在野外进行分析 型小鼠、NKT细胞缺陷型小鼠和NKT细胞缺陷型小鼠 用野生型NKT细胞或缺乏效应子功能的NKT细胞转移 使用细胞免疫学和组织学技术。完成这些 aims将为NKT细胞在保护性免疫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.