APOPTOSIS/TOLERANCE/MAINTENANCE OF IMMUNITY

细胞凋亡/耐受/免疫维持

• 批准号: 6384541
• 负责人: Thomas Almon Ferguson
• 金额: $ 38.5万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6384541
• 关键词: T cell receptor; T lymphocyte; anterior chamber; antigen antibody reaction; antigen presenting cell; apoptosis; clone cells; cytokine; eye disorder; fluorescence microscopy; hybridomas; immune tolerance /unresponsiveness; immunopathology; immunoregulation; integrins; laboratory mouse; leukocyte activation /transformation; leukocyte adhesion molecules; mixed tissue /cell culture; polymerase chain reaction

DESCRIPTION (Investigator's Abstract): This laboratory has been actively engaged in the study of the eye as an immunologically privileged site using the ACAID model of immunoregulation (ACAID) for Anterior Chamber Associated Immune Deviation). In general, following the introduction of a variety of antigens into the eye, cell mediated responses are actively suppressed, while antibody responses are normal or elevated. It has been shown that this pattern of responses is due to aggressive regulation by various populations of T-cells (10-13) and antigen presenting cells (14). Previous studies from the laboratory have extensively characterized the Ts-cells involved in ACAID, identified a serum borne factor that mediates ACAID, located an antigen presenting cell for TNP-ACAID, identified several cytokines involved in ACAID, and demonstrated that light regulates the suppressed DTH response in ACAID. It is the purpose of these studies to continue this work and further analyze the regulation of the ocular immune response. The investigators will first examine the role of adhesion molecules in the activation of T-cell in the eye. Specifically, T-cell integrins such as VLA-VLA-5, LFA-1, as well as ICAM-1 will be studied by using small synthetic peptides and antibodies that block their function. These types of studies have important implications for drug design. Studies will be done to continue the analysis of the soluble mediators in ACAID. The investigators will also determine the role of T-cell derived cytokine, complement component C5, and soluble T-cell receptor in the ACAID system. In addition, they will look at the regulation of the antibody response following anterior chamber injection of antigen. Understanding the relationship between the immune system and the eye has important implications for the control and treatment of ocular disease.

描述（调查员的摘要）：该实验室已经积极 使用视线作为免疫学特权网站的研究 与前腔相关的免疫调节的ACAID模型（ACAID） 免疫偏差）。 通常，在引入各种 抗原进入眼睛，细胞介导的反应被积极抑制， 而抗体反应正常或升高。 已经表明 这种响应模式是由于各种的积极调节 T细胞（10-13）和抗原呈递细胞的种群（14）。以前的 实验室的研究已经广泛表征了TS细胞 参与ACAID，确定了介导ACAID的血清寄生因素， 位于TNP ACAID的抗原呈现细胞，确定了几个 涉及ACAID的细胞因子，并证明光调节 抑制ACAID中的DTH响应。这些研究的目的是 继续这项工作，并进一步分析眼部免疫的调节 回复。 研究人员将首先检查粘附的作用 眼睛中T细胞激活的分子。 具体而言，T细胞 诸如VLA-VLA-5，LFA-1以及ICAM-1之类的整合素 使用小的合成肽和阻断其功能的抗体。 这些类型的研究对药物设计具有重要意义。 将进行研究以继续对可溶性介体进行分析 Acaid。 研究人员还将确定T细胞得出的作用 Acaid中的细胞因子，补体成分C5和可溶性T细胞受体 系统。 另外，他们将研究抗体的调节 抗原前腔注射后的反应。 理解 免疫系统与眼睛之间的关系很重要 对眼部疾病的控制和治疗的影响。