MECHANISMS OF ORAL TOLERANCE IN HEALTH AND IN IBD

健康和 IBD 中的口服耐受机制

• 批准号: 2372459
• 负责人: BRUCE E SANDS
• 金额: $ 8.55万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2372459
• 关键词: Crohn's disease; T lymphocyte; antigen presentation; cellular immunity; clinical research; delayed hypersensitivity; disease /disorder etiology; drug administration routes; human subject; humoral immunity; inflammatory bowel diseases; inhalation drug administration; mucosal immunity; nutrition; nutrition related tag; oral tolerance; skin hypersensitivity; smoking; ulcerative colitis

DESCRIPTION (Taken from application) Oral tolerance is the phenomenon of specific systemic tolerance established after ingestion of an antigen. Mounting evidence indicates that oral tolerance regimens may be a useful approach in the treatment of immunemediated diseases. Oral tolerance may therefore be considered as a possible novel mode of therapy for ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease (IBD). However, since intestinal immunity is abnormal in IBD, it is unclear if oral tolerance would be an effective therapeutic strategy for these diseases. As the basis for future therapeutic trials of oral tolerance in IBD, the hypothesis that oral tolerance is aberrant in IBD will be tested. This will be accomplished by comparing healthy subjects and patients with Crohn's disease or ulcerative colitis with regard to their ability to achieve specific systemic T cell tolerance after a regimen of antigen ingestion. The effect of prior feeding upon the subsequent development of specific systemic T cell tolerance, as measured by antigen-specific T cell proliferation and skin delayed hypersensitivity will be compared. The effects of disease characteristics, as well as nutritional state, age, gender, smoking history, and history of prior appendectomy on the development of oral tolerance will also be explored in order to define appropriate inclusion criteria for future clinical trials. As an alternative approach, a regimen of nasal inhalation will investigated as a means of achieving systemic tolerance. This will permit testing of the hypothesis that aberrant oral tolerance in IBD is a consequence of altered intestinal mucosal function, and could provide an alternate route of administration for use in therapeutic protocols. Finally, appropriate candidate antigens and laboratory endpoints for tolerance regimens will be identified. The data obtained in these investigations should provide sufficient background to permit the design of a therapeutic trial of mucosal tolerance, whether by oral or nasal route, in IBD.

描述（取自应用程序） 口服公差是建立的特定全身耐受性的现象 摄入抗原后。 安装证据表明口头 公差方案可能是治疗的有用方法 免疫疾病。 因此，口服耐受性可能被认为是 可能用于溃疡性结肠炎和克罗恩病的新型治疗方式， 两种主要形式的炎症性肠病（IBD）。 但是，自从 intestinal immunity is abnormal in IBD, it is unclear if oral tolerance 对于这些疾病，将是有效的治疗策略。 作为基础 对于IBD中口服耐受性的将来的治疗试验，这是一个假设 IBD中的口服耐受性异常。 这将完成 通过比较健康的受试者和克罗恩病的患者或 溃疡性结肠炎就其实现特定的系统性的能力 抗原摄入方案后的T细胞耐受性。 先验的效果 以随后的特定全身T细胞的发展为食 耐受性，通过抗原特异性T细胞增殖和皮肤测量 将比较延迟的超敏反应。 疾病的影响 特征以及营养状态，年龄，性别，吸烟史， 和先前关于口服耐受性发展的阑尾切除术的历史 还可以探索以定义适当的纳入标准 未来的临床试验。 As an alternative approach, a regimen of nasal inhalation will investigated 作为实现系统性宽容的一种手段。 这将允许测试 假设IBD中异常口服耐受性是改变的结果 肠粘膜功能，可以提供 用于治疗方案的管理。 最后，适当 候选抗原和实验室的耐受性方案将是 确定。 这些调查中获得的数据应提供 足够的背景允许设计粘膜治疗试验 IBD中的耐受性，无论是口头还是鼻路线。