IMMUNOPATHOGENESIS OF ARTHRITIS IN MRL MICE

自身免疫性MRL-1PR小鼠发生关节病 类风湿性关节炎的共同组织学特征 (RA)。为了阐明这种自发性疾病的免疫发病机制 疾病模型，建议识别效应器机制 通过遗传和细胞分析。1PR同源基因小鼠和 将对信息丰富的F1和F2世代进行研究，以确定 1PR本身是否足以治疗关节炎或需要相互作用 与其他基因有关。为了评估疾病的细胞机制，MRL- 1PR小鼠将接受各种免疫调节剂的治疗 如抗L3T4和Ia抗原的单抗。这个 未处理和未处理的滑膜组织中细胞的性质 治疗后的小鼠将用免疫组织学方法进行研究 用于表征细胞表面标记的技术。制作 滑膜中细胞因子的含量也将通过原位方法进行评估 使用针对各种介体的探针进行杂交 假定是为了促进联合变化。最后，MRL的发现- 1PR小鼠将与观察到的 胶原性关节炎，T细胞在其中的作用是 更清晰的定义。总而言之，这些研究应该有助于阐明 MRL-1PR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.