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RHEUMATOID ARTHRITIS AND LYME DISEASE--T CELL RECEPTOR

类风湿性关节炎和莱姆病--T细胞受体

基本信息

批准号：
3457028
负责人：
STEVEN J PADULA
金额：
$ 10.92万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 1994-06-30
项目状态：
已结题

项目摘要

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接触。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。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effects of H-7 are not exclusively mediated through protein kinase C or the cyclic nucleotide-dependent kinases.

H-7 的作用不仅仅通过蛋白激酶 C 或环核苷酸依赖性激酶介导。

DOI：
10.1016/0006-291x(89)91973-6
发表时间：
1989
期刊：
Biochemical and biophysical research communications
影响因子：
3.1
作者：
LoveJr,JT;Padula,SJ;Lingenheld,EG;Amin,JK;Sgroi,DC;Wong,RL;Sha'fi,RI;Clark,RB
通讯作者：
Clark,RB

Identification of encephalitogenic V beta-4-bearing T cells in SJL mice. Further evidence for the V region disease hypothesis?

SJL 小鼠中携带脑炎 V beta-4 的 T 细胞的鉴定。

DOI：
发表时间：
1991
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Padula,SJ;Lingenheld,EG;Stabach,PR;Chou,CH;Kono,DH;Clark,RB
通讯作者：
Clark,RB

Subtypes of helper cells. Non-inflammatory type 1 helper T cells.

辅助细胞的亚型。

DOI：
发表时间：
1988
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Wong,RL;Ruddle,NH;Padula,SJ;Lingenheld,EG;Bergman,CM;Rugen,RV;Epstein,DI;Clark,RB
通讯作者：
Clark,RB

An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis.