IMMUNOGENETIC STUDIES OF COLLAGEN ARTHRITIS

胶原蛋白诱导的关节炎(CIA)是一种新的慢性自身免疫性关节炎模型 周围性关节炎。我们观察到了菌株的差异 11人对CIA的易感性和对胶原(II)的免疫应答 代表6个RT1A特异性的近交系大鼠。我们的目标 是：1)描述基因控制的免疫功能，调节 胶原性关节炎大鼠模型。我们将确定是否存在差异 易感性与程度、类型或 胶原蛋白免疫反应的特异性(II)。要确定 连锁，控制RT1.A异型的基因的遗传模式， 表型对CIA的易感性和胶原特异性免疫反应 将在F1、F2和回交后代之间进行分析 敏感和耐药的同源菌株。耐药菌株将是 成人胸腺切除术检测胶原特异性抑制细胞活性 和环磷酰胺前处理。2)确定(推定的)关节炎 胶原蛋白(II)分子的决定因素。我们会比较免疫力 耐药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。抗体效价 均采用酶联免疫吸附试验测定。细胞免疫功能将通过体外实验进行评估 脾细胞增殖实验。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细胞进行检测 通过尼龙毛线柱。天然II型胶原蛋白(大鼠、小牛、 雏鸡)、它们的溴化氰多肽和胶原酶(哺乳动物) 产生的螺旋片段将被用作抗原和免疫原。3)至 建立滑膜细胞相互作用的组织培养模型， 胶原蛋白，以及胶原蛋白自身反应性淋巴细胞可以在 体外培养。关节炎大鼠滑膜细胞原代培养的制备 膝关节组织。我们将确定胶原(II)，CNBR的作用 多肽和胶原激活的单个核细胞对增殖的影响 (~3H-胸腺嘧啶核苷摄取)、胶原酶产生和Intelukin 2 制作。所需的菌株在我们的老鼠群体中可用，包括 4对CIA不一致的同源染色对。这项研究将提供 与抗胶原自身免疫活性相关的信息在 类风湿性关节炎患者。

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.