IMMUNOGENETIC STUDIES OF COLLAGEN ARTHRITIS

胶原关节炎的免疫遗传学研究

• 批准号: 3152124
• 负责人: Marie M. Griffiths
• 金额: $ 9.49万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1986-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3152124
• 关键词: T lymphocyte; autoimmune disorder; cell cell interaction; cellular immunity; collagenase; disease /disorder model; enzyme linked immunosorbent assay; genetic regulation; humoral immunity; immunogenetics; immunoregulation; interleukin 2; leukocyte activation /transformation; rheumatoid arthritis; tissue /cell culture

Collagen-induced arthritis (CIA) is a new, autoimmune model of chronic peripheral arthritis. We have observed strain differences in susceptibility to CIA and in immune response to collagen (II) among 11 inbred rat strains representing 6 RT1.A specificities. Our objectives are: 1) to delineate genetically controlled immune functions that regulate collagen-arthritis in rats. We will determine if differences in susceptibility are related to differences in the degree, type, or specificity of the immune response to collagen (II). To determine linkages, the inheritance pattern of genes controlling RT1.A allotypes, phenotypic susceptibility to CIA, and collagen-specific immune responses will be analyzed among the F1, F2, and backcross progeny of matings between susceptible and resistant, congenic strains. Resistant strains will be tested for collagen-specific suppressor cell activity by adult thymectomy and cyclophosphamide pretreatment. 2) To identify (putative) arthritogenic determinants on the collagen (II) molecule. We will compare the immune response of resistant and susceptible strains to collagen (II) fragments. We will also test these polypeptides as inducers of CIA. Antibody titers are determined by ELISA. Cellular immunity will be assessed by in vitro spleen cell proliferation assays. Antigen-specific, T-cell proliferation will be measured using sensitized peritoneal exudate T-cells purified by passage through nylon wool columns. Native type II collagens (rat, calf, chick), their cyanogen-bromide peptides, and collagenase (mammalian) produced helical fragments will be used as antigens and immunogens. 3) To establish a tissue culture model whereby the interaction of synovial cells, collagen, and collagen auto-reactive lymphoid cells can be investigated in vitro. Primary synovial cell cultures will be prepared from arthritic rat knee joint tissues. We will determine the effects of collagen (II), CNBr peptides, and collagen-activated mononuclear cells on proliferation (3H-thymidine uptake), collagenase production, and Inteleukin 2 production. The strains needed are available in our rat colony and include 4 CIA-discordant, congenic stain pairs. This study will provide information relative to the role of anti-collagen autoimmune activity in patients with rheumatoid arthritis.

胶原诱导性关节炎（CIA）是一种新的慢性自身免疫性关节炎模型， 周围性关节炎 我们已经观察到了 在11名受试者中， 代表6种RT1.A特异性的近交系大鼠品系。 我们的目标 是：1）描述遗传控制的免疫功能，调节 大鼠胶原性关节炎。 我们将确定， 易感性与程度、类型或 免疫反应对胶原蛋白的特异性（II）。 以确定 连锁，控制RT1.A同种异型的基因的遗传模式， CIA的表型易感性和胶原特异性免疫应答 将在F1、F2和回交后代中进行分析， 敏感和耐药的同类菌株。 耐药菌株将是 通过成人胸腺切除术检测胶原特异性抑制细胞活性 环磷酰胺预处理。 2)识别（假定）致关节炎性 胶原蛋白（II）分子上的决定簇。 我们将比较免疫的 抗性和敏感菌株对胶原蛋白（II）片段的反应。 我们还将测试这些多肽作为CIA的诱导剂。 抗体滴度 通过ELISA测定。 将通过体外试验评估细胞免疫力。 脾细胞增殖测定。 抗原特异性，T细胞增殖 将使用经纯化的致敏腹膜渗出液T细胞测量 穿过尼龙羊毛柱。 天然II型胶原蛋白（大鼠，小牛， 鸡）、其溴化氰肽和胶原酶（哺乳动物） 产生的螺旋片段将用作抗原和免疫原。 3)到 建立组织培养模型， 胶原和胶原自身反应性淋巴样细胞可以在 体外 将从关节炎大鼠制备原代滑膜细胞培养物 膝关节组织。 我们将确定胶原蛋白（II），CNBr 肽和胶原活化的单核细胞对增殖的影响 （3 H-胸苷摄取）、胶原酶产生和Inteleukin 2 生产 所需的菌株可在我们的鼠群中获得，包括 4个CIA不一致的同源染色对。 本研究将提供 关于抗胶原自身免疫活性在 类风湿性关节炎患者。

项目成果

Effects of rat cytomegalovirus infection on immune functions in rats with collagen induced arthritis.

大鼠巨细胞病毒感染对胶原诱导性关节炎大鼠免疫功能的影响。

• 发表时间: 1991
• 期刊: The Journal of rheumatology
• 作者: Griffiths,MM;Smith,CB;Wei,LS;Ting-Yu,SC
• 通讯作者: Ting-Yu,SC

Genetic control of collagen-induced arthritis in rats: the immune response to type II collagen among susceptible and resistant strains and evidence for multiple gene control.

胶原诱导的大鼠关节炎的基因控制：易感菌株和耐药菌株对 II 型胶原的免疫反应以及多基因控制的证据。

• 发表时间: 1984
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Griffiths,MM;DeWitt,CW
• 通讯作者: DeWitt,CW

Immunogenetics of collagen-induced arthritis in rats.

• DOI: 10.3109/08830188809044766
• 发表时间: 1988-09-01
• 期刊: International reviews of immunology
• 影响因子: 5
• 作者: Griffiths, M M

Rat cytomegalovirus infection enhances type II collagen arthritis in rats.

大鼠巨细胞病毒感染可增强大鼠 II 型胶原关节炎。

• DOI: 10.1002/art.1780291012
• 发表时间: 1986
• 期刊: Arthritis and rheumatism
• 作者: Smith,CB;Griffiths,MM;Wei,LS
• 通讯作者: Wei,LS

Modulation of collagen-induced arthritis in rats by non-RT1-linked genes.

非 RT1 连锁基因调节大鼠胶原诱导的关节炎。

• 发表时间: 1984
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Griffiths,MM;DeWitt,CW
• 通讯作者: DeWitt,CW