RHEUMATOID ARTHRITIS AND LYME DISEASE--T CELL RECEPTOR

类风湿性关节炎和莱姆病--T细胞受体

• 批准号: 3457024
• 负责人: STEVEN J PADULA
• 金额: $ 6.84万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3457024
• 关键词: CD3 molecule; Lyme disease; Spirochaetales; T cell receptor; T lymphocyte; alleles; antireceptor antibody; autoimmune disorder; clone cells; gene mutation; human subject; laboratory mouse; molecular pathology; monoclonal antibody; nucleic acid hybridization; rheumatoid arthritis; surface antigens; synovitis

T cells appear to play a role in the pathogenesis of rheumatoid arthritis although there has been no demonstration of T cell reactivity to putative disease-related antigens. Recent advances in the understanding of the structure and genetics of the T cell antigen-receptor have made available new approaches to the study of T cell specificity. In this proposal T cell clones will be derived from the synovial space (SS) of a well defined subset of RA patients, i.e. classical or definite RA with proliferative synovitis. The disease-specific T cell clones will be identified from among the heterogeneous clones derived from this site of inflammation on the basis of finding a clonal or oligoclonal distribution of antigen receptor gene rearrangements. T cells derived from the SS of patients with Lyme arthritis will be similarly studied as a model in which the disease related antigen is known. Interleukin-2 dependent T cell clones from the SS and the peripheral blood will be derived from patients with Lyme arthritis and RA. In the case of Lyme arthritis, T cell clones will be grown with the causative agent, B. burgdorferi. In addition, T cell clones will be grown in parallel with anti-T3 antibody to further confirm that anti-T3 antibody can maintain the antigen- specificity of T cell lines grown in the absence of specific antigens. In the case of RA, T cell clones will be grown only with anti-T3 antibody. T cell receptor rearrangements utilized by these T cell clones will be studied by using Southern blot analysis (including pulse-field electrophoresis for the alpha chain) and DNA sequencing. The long-term goal of the present proposal is to identify the disease-specific T cells derived from the synovial space in RA and generate monoclonal antibodies directed toward the T cell receptor on such cells. Such antibodies would be of theoretical, diagnostic, and perhaps therapeutic significance.

T细胞似乎在类风湿的发病机制中起作用 关节炎，尽管还没有T细胞的表现 对假定的疾病相关抗原的反应性。 近几年来对该结构的理解和研究进展 T细胞抗原受体的遗传学已经提供了新的 研究T细胞特异性的方法。在本提案T中 细胞克隆将来自井的滑膜间隙(SS) 类风湿性关节炎患者的定义子集，即典型或明确的类风湿关节炎 增生性滑膜炎。疾病特异性T细胞克隆将是 从从此派生的异类克隆中标识 在找到克隆或寡克隆的基础上发现炎症部位 抗原受体基因重排的分布。T细胞 从SS派生的莱姆关节炎患者会 类似地被研究为疾病相关抗原的模型 是已知的。 白介素2依赖的T细胞克隆 外周血将来自莱姆关节炎患者 和RA。在莱姆关节炎的情况下，T细胞克隆将被培养出来 与病原体伯格多尔费里。此外，T细胞 克隆将与抗T3抗体平行生长，以进一步 确认抗T3抗体能维持抗原- T细胞系在缺乏特异性的情况下生长的特异性 抗原。在RA的情况下，T细胞克隆将仅在 抗T3抗体。利用T细胞受体重排 这些T细胞克隆将通过Southern印迹分析进行研究 (包括阿尔法链的脉冲场电泳法)和 DNA测序。 本提案的长期目标是确定 类风湿关节炎和类风湿性关节炎患者滑膜间隙来源的疾病特异性T细胞 产生针对T细胞的单抗 这些细胞上的受体。这样的抗体将是理论上的， 具有诊断意义，或许还有治疗意义。