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: 3457027
• 负责人: STEVEN J PADULA
• 金额: $ 11.09万
• 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/3457027
• 关键词: Borrelia; CD3 molecule; T cell receptor; T lymphocyte; alleles; antireceptor antibody; autoimmune disorder; borreliosis; cellular immunity; clone cells; gene mutation; human subject; laboratory mouse; molecular pathology; monoclonal antibody; rheumatoid arthritis; southern blotting; 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