IMMUNOREGULATORY CIRCUITS IN MAN

人类的免疫调节回路

• 批准号: 6549733
• 负责人: Chikao Morimoto
• 金额: $ 22.77万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 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/6549733
• 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（改编自研究者摘要）：记忆CD 4 T细胞发挥作用 在宿主防御以及触发和维持 炎症 共刺激信号的触发起着中枢作用， 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，CD 29/VLA，CD 26和CD 27已经被建立， 这个团体。 CD 29/VLA和CD 26在CD 4记忆上优先表达 T细胞，并在共刺激，功能， 记忆T细胞的迁移。 在这方面，仍有许多问题有待澄清。 CD 29/VLA和CD 26在信号转导中的复杂功能及CD 29/VLA和CD 26在细胞凋亡中的作用 对T细胞功能和细胞迁移的后续影响。 的主要目标 本申请的目的是确定人的免疫调节回路。 本申请的具体目的是：1） CD 29/VLA在T细胞共刺激、信号传导和T细胞功能中的作用 他们将 确定Cas-L酪氨酸磷酸化和FAK的结构基础 激活并确定Cas-L在CD 29/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细胞中的作用也被证实。 移民将被定义。 2)CD 26/DPPIV在T细胞中的分子基础 功能和共刺激。 CD 26/DPPIV在T细胞迁移中的作用， ADA与CD 26结合的精确特征，以及ADA与CD 26结合的功能特性。 将定义ADA在T细胞活化中的意义。 此外该 将定义除ADA之外的CD 26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介导的共刺激信号分析 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， 测定 此外，血清/血浆中CD 26/DPPIV水平及其 与自身免疫性疾病的临床并发症的相关性将是 定义了 这项研究不仅将为理解 T细胞活化和迁移的机制，但也将提供新的 深入了解免疫的精确分子机制 在各种自身免疫性疾病中发现的异常， 制定合理的治疗方法， 发现于此类疾病中。