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: 3457026
• 负责人: STEVEN J PADULA
• 金额: $ 10.83万
• 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/3457026
• 关键词: Borrelia; CD3 molecule; T cell receptor; T lymphocyte; alleles; antireceptor antibody; autoimmune disorder; borreliosis; 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细胞似乎在类风湿性关节炎的发病机制中发挥作用 关节炎，虽然没有证据表明T细胞 对推定的疾病相关抗原的反应性。 对结构的认识和 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。 在本提案中，T 细胞克隆将从孔的滑膜间隙（SS）中获得 RA患者的定义子集，即典型或明确的RA伴 增生性滑膜炎 疾病特异性T细胞克隆将被 从来源于此的异源克隆中鉴定出 炎症部位的基础上找到一个克隆或寡克隆 抗原受体基因重排的分布。 T细胞 来自莱姆关节炎患者的SS将是 类似地作为模型进行研究，其中疾病相关抗原 是已知的。 来自SS和T细胞的白细胞介素-2依赖性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细胞克隆将生长 与病原体B。burgdorferi。 此外，T细胞 克隆将与抗T3抗体平行生长，以进一步 证实抗T3抗体可维持抗原- 特异性T细胞系生长在缺乏特异性 抗原 在RA的情况下，T细胞克隆将仅在具有以下条件的情况下生长： 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α链的脉冲场电泳）和 DNA测序 本提案的长期目标是确定 来源于RA滑膜间隙的疾病特异性T细胞， 产生针对T细胞的单克隆抗体 这些细胞上的受体。 这种抗体是理论上的， 诊断，也许还有治疗意义。