IMMUNOREGULATORY CIRCUITS IN MAN

描述(改编自研究人员摘要)：记忆中的CD4T细胞发挥作用 在宿主防御以及触发和维护 发炎。共刺激信号的触发起到了中心作用 在产生有效的免疫反应方面发挥作用。共刺激作用 信号可以由许多辅助分子提供。中的 共刺激分子CD29/VLA、CD26和CD27已经由 这群人。CD29/VLA和CD26在CD4记忆体上优先表达 T细胞在共刺激、功能和免疫调节中发挥重要作用。 记忆T细胞的迁移。关于这一点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及其机制 对T细胞功能和细胞迁移的后续影响。主要目标是 这一应用的目的是确定人的免疫调节回路。 本申请的具体目的是：1)分子基础 CD29/VLA在T细胞共刺激、信号转导和T细胞功能中的作用他们会 确定CaS-L酪氨酸磷酸化和FAK的结构基础 Cas-L在CD29/VLA介导的细胞因子中的激活及作用 生产和基因表达。此外，CaS-L在T细胞中的作用 将定义迁移。2)CD26/DPPIV在T细胞中的分子基础 功能和共刺激作用。CD26/DPPIV在T细胞迁移中的作用 ADA与CD26结合的精确特征及其功能 ADA在T细胞激活中的意义将被明确。此外， 将定义除ADA以外的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介导的共刺激作用分析 将会被执行。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 下定决心。此外，血清/血浆中CD26/DPPIV水平及其与CD26/DPPIV的相关性 与自身免疫性疾病临床并发症的相关性将是 已定义。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 对理解免疫的精确分子机制的见解 在各种自身免疫性疾病中发现的异常，并将导致 畸形手法的合理治疗进展 在这类疾病中发现。

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.