IMMUNOREGULATORY CIRCUITS IN MAN

人类的免疫调节回路

• 批准号: 2692931
• 负责人: Chikao Morimoto
• 金额: $ 28.21万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2692931
• 关键词: CD antigens; Sjogren's syndrome; T lymphocyte; autoradiography; biological signal transduction; cell migration; cytokine; enzyme linked immunosorbent assay; gene expression; human subject; immunoregulation; laboratory mouse; leukocyte activation /transformation; phosphorylation; protein biosynthesis; protein tyrosine kinase; rheumatoid arthritis; systemic lupus erythematosus; tissue /cell culture

DESCRIPTION (Adapted from Investigator's abstract): Memory CD4 T-cells play a key role in host defense as well as the triggering and maintaining of inflammation. The triggering of the costimulatory signals plays a central role in the generation of effective immune responses. The costimulatory signals can be provided by a number of accessory molecules. Of the costimulatory molecules, CD29/VLA, CD26, and CD27 have been established by this group. CD29/VLA and CD26 are preferentially expressed on CD4 memory T-cells and play an important role in the costimulation, function, and migration of memory T-cells. Much remains to be clarified regarding the complex functions of CD29/VLA and CD26 in signal transduction and the subsequent effects upon T-cell function and cell migration. The major goal of this application is to determine the immunoregulatory circuits in man. The specific aims of this application are: 1) The molecular basis of CD29/VLA in T-cell costimulation, signaling and T-cell function. They will define the structural basis of Cas-L tyrosine phosphorylation and FAK activation and define the role of Cas-L in CD29/VLA-mediated cytokine production and gene expression. Moreover, the role of Cas-L in T-cell migration will be defined. 2) The molecular basis of CD26/DPPIV in T-cell function and costimulation. The role of CD26/DPPIV in T-cell migration, the precise characteristics of the binding of ADA to CD26, and the functional significance of ADA in T-cell activation will be defined. In addition, the structure and function of the ligand of CD26 other than ADA will be defined. 3), The molecular and cellular defects in patients with autoimmune diseases. Analysis of VLA-mediated costimulation in patients with autoimmune diseases will be performed. Moreover, the expression and function, of Cas-L, and FAK as well as the migratory activity of T-cells in autoimmune diseases will be determined. In addition, the level of CD26/DPPIV in serum/plasma and its correlation with clinical complications in autoimmune diseases will be defined. The study will not only provide new insights into understanding of the mechanisms of T-cell activation and migration, but will also provide new insights into understanding the precise molecular mechanisms of immune abnormalities found in various autoimmune diseases and will lead to the development of rational therapy for the manipulation of the abnormalities found in such diseases.

描述（改编自研究者的摘要）：记忆 CD4 T 细胞发挥作用 在宿主防御以及触发和维持中发挥关键作用 炎。 共刺激信号的触发起着核心作用 在产生有效免疫反应中的作用。 共刺激 信号可以由许多辅助分子提供。 的 共刺激分子 CD29/VLA、CD26 和 CD27 已由 这个组。 CD29/VLA 和 CD26 优先在 CD4 内存上表达 T 细胞在共刺激、功能和 记忆 T 细胞的迁移。 关于该问题还有很多需要澄清的地方 CD29/VLA 和 CD26 在信号转导中的复杂功能和 随后对 T 细胞功能和细胞迁移产生影响。 主要目标 该应用的目的是确定人体的免疫调节回路。 该应用的具体目标是： 1) 的分子基础 CD29/VLA 在 T 细胞共刺激、信号传导和 T 细胞功能中的作用。 他们会 定义 Cas-L 酪氨酸磷酸化和 FAK 的结构基础 激活并定义 Cas-L 在 CD29/VLA 介导的细胞因子中的作用 生产和基因表达。 此外，Cas-L 在 T 细胞中的作用 迁移将被定义。 2) T细胞中CD26/DPPIV的分子基础 功能和共刺激。 CD26/DPPIV 在 T 细胞迁移中的作用 ADA 与 CD26 结合的精确特征，以及功能 ADA 在 T 细胞激活中的重要性将被定义。 此外， 将定义除ADA之外的CD26配体的结构和功能。 3）、自身免疫性疾病患者的分子和细胞缺陷。 自身免疫性疾病患者 VLA 介导的共刺激分析 将被执行。 此外，Cas-L和FAK的表达和功能 以及自身免疫性疾病中 T 细胞的迁移活性 决定。 另外，血清/血浆中CD26/DPPIV的水平及其 与自身免疫性疾病临床并发症的相关性 定义的。 该研究不仅为理解 T 细胞激活和迁移的机制，但也将提供新的 深入了解免疫的精确分子机制 各种自身免疫性疾病中发现的异常，会导致 开发合理的治疗方法来控制异常 发现于此类疾病。