IMMUNOPATHOGENESIS OF ARTHRITIS IN MRL MICE

自身免疫MRL-1 pr小鼠发生具有临床症状的关节病 与类风湿性关节炎相同的组织学特征 （RA）。 为了阐明这种自发性的免疫发病机制， 疾病模型，建议识别效应机制 通过基因和细胞分析。 1 pr同源小鼠， 将对信息丰富的F1和F2代进行研究，以确定 1 pr本身是否足以治疗关节炎或需要相互作用 与其他基因。 为了评估疾病的细胞机制，MRL- 将用各种免疫调节剂处理1 pr小鼠 如抗L3 T4和Ia抗原的单克隆抗体。 的 在未治疗和未治疗的患者中， 然后使用免疫组织化学方法研究治疗的小鼠。 技术来表征细胞表面标志物。 生产 还将通过原位杂交在滑膜中评估细胞因子的水平。 使用针对各种介质的探针的杂交， 以促进共同的变化。 最后，MRL的结果- 将1 pr小鼠与在具有以下特征的小鼠中观察到的那些进行比较： 胶原诱导的关节炎，一种模型，其中T细胞的作用是 更明确。 总之，这些研究应该有助于阐明 MRL-1 pr关节炎的重要方面，并帮助评估其 与RA关节中发生的过程的关系。

Autoimmune MRL-1pr mice develop an arthropathy with clinical and histological features in common with rheumatoid arthritis (RA). To elucidate the immunopathogenesis of this spontaneous disease model, it is proposed to identify effector mechanisms through genetic and cellular analysis. 1pr congenic mice and informative F1 and F2 generations will be studied to determine whether 1pr is itself sufficient for arthritis or requires interaction with other genes. To assess cellular mechanisms of disease, MRL- 1pr mice will be treated with various immunomodulatory agents such as monoclonal antibodies to L3T4 and Ia antigens. The nature of the cells infiltrating the synovium in both untreated and treated mice will then be investigated using immunohistologic techniques to characterize cell surface markers. The production of cytokines will also be evaluated in the synovium by in situ hybridization using probes for various mediators that have been postulated to promote joint changes. Finally, findings with MRL- 1pr mice will be compared with those observed in mice with collagen-induced arthritis, a model in which the role of T-cells is more defined. Together, these studies should help elucidate important facets of MRL-1pr arthritis and help assess its relationship to processes occurring in the RA joint.