SUPERANTIGENS, MAST CELLS AND T CELLS IN ATOPIC DISEASE

特应性疾病中的超抗原、肥大细胞和 T 细胞

• 批准号: 2470289
• 负责人: CHARITY C FOX
• 金额: $ 6.93万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2470289
• 关键词: MHC class II antigen; T lymphocyte; antigen antibody reaction; antigen presentation; atopic dermatitis; bacterial antigens; bacterial proteins; blocking antibody; cell cell interaction; cell line; cellular immunity; crosslink; cytokine; density gradient ultracentrifugation; flow cytometry; human tissue; inflammation; interleukin 4; leukocyte activation /transformation; mast cell; mixed tissue /cell culture; superantigens; virus protein

DESCRIPTION (adapted from applicant's abstract): Superantigens are bacterial and viral proteins that can mediate non-specific activation of T cells by crosslinking of T cell receptor V beta region sequences with the MHC class II molecules on accessory cells. The staphylococcal enterotoxins A and B (SEA, SEB) have been identified in cultures from the skin of patients with chronic atopic dermatitis (AD) and are thought to promote T cell proliferation in AD. The T cells in AD are predominantly of the Th2 phenotype. Mast cells have been implicated as a source of IL-4 that can drive this Th2 response, since degranulation of mast cells is a prominent feature of atopic inflammation. However, the mechanism by which superantigens stimulate mast cells to release IL-4 and other mediators is unclear. This project is based on the hypothesis that mast cells are stimulated during interactions with superantigen and T cells and subsequently release IL-4 and other mediators found in atopic inflammation. The applicant will study the ability of mast cells to present superantigen via their MHC class II molecules as well as the ability of mast cells to drive a Th2 response. Specifically, the applicant will determine the cytokine profiles of T cells and mast cells following in vitro stimulation of peripheral T cells with a mast cell line presenting superantigens. She will investigate (1) whether modulation of mast cell function by cytokines influences the ability of mast cells to present superantigen and (2) whether superantigen activation of mast cells occurs through MHC class II molecule crosslinking. Finally, she will determine whether AD T cells respond differently than normal T cells to superantigen stimulation.

描述（改编自申请人的摘要）：超抗原是 细菌和病毒蛋白可以介导非特异性激活T 通过与T细胞受体Vβ区域序列的交联细胞 辅助细胞上的MHC II类分子。 葡萄球菌肠毒素 A和B（SEA，SEB）已在皮肤的培养物中鉴定出来 患有慢性特征性皮炎（AD）的患者，被认为会促进T AD中的细胞增殖。 AD中的T细胞主要是TH2 表型。 肥大细胞已被认为是可以的IL-4来源 驱动此Th2响应，因为肥大细胞的脱粒是突出的 特应炎症的特征。 但是，该机制 超抗原刺激肥大细胞释放IL-4和其他介体是 不清楚。 该项目基于刺激肥大细胞的假设 在与超抗原和T细胞的相互作用期间，随后释放 IL-4和其他介体在特应炎症中发现。 申请人将 研究肥大细胞通过其MHC类呈现超抗原的能力 II分子以及肥大细胞驱动Th2反应的能力。 具体而言，申请人将确定T细胞的细胞因子特征 和肥大细胞在体外刺激周围T细胞中 肥大细胞系呈现超抗原。 她将调查（1）是否 细胞因子对肥大细胞功能的调节会影响桅杆的能力 细胞呈现超抗原和（2）超抗原激活是否激活 肥大细胞通过MHC II类分子交联发生。 最后，她 将确定AD T细胞的反应与正常T细胞的反应是否不同 超抗原刺激。