CHRONIC GVH DISEASE IN RAT RADIATION CHIMERAS

慢性移植物抗宿主病(GVHD)是一种经常使人衰弱和 异基因骨髓移植受者通常会出现致命的并发症。它 显示了自身免疫性疾病的许多特征，如硬皮病， 干燥综合征和原发性胆汁性肝硬变。尽管许多人免疫 异常与慢性移植物抗宿主病有关，其发病机制 仍然不为人知。 大鼠放射性嵌合体中自发和快速诱导的慢性移植物抗宿主病 在临床和组织学上与急性移植物抗宿主病不同，但非常相似 人类的慢性移植物抗宿主病。使用这些多种模型，我们已经开始 在了解慢性GVHD方面取得进展。蜂窝 用单抗进行的免疫病理学研究表明，靶点 组织(皮肤和肝脏)以辅助表型细胞为主。 (W3/25)。与急性移植物抗宿主病相比，这些组织具有优势 非辅助性T淋巴细胞(OX8)。在皮肤内部，帮助者 慢性移植物抗宿主病的表型细胞位于真皮内，而急性移植物抗宿主病的表型细胞 移植物抗宿主病表皮中有大量非辅助性细胞(OX8)。 通过比较多种慢性肾衰模型的免疫功能异常 GVHD，我们已经能够分离出一些不一致的在场 所有模型中都存在来自其他异常的异常。因此， 皮肤IgM沉积和血管炎似乎是不必要的 胸腺髓质改变与非特异性抑制因子 细胞在病理上可能是重要的。目前的研究是 专注于确定必要的抗原差异和组织 抗原差异的位置，必要的淋巴细胞群，以及 免疫缺陷与直接免疫损伤在疾病中的相对作用 产生慢性移植物抗宿主病。(TT)

Chronic graft-versus-host disease (GVHD) is a frequently debilitating and often fatal complication in recipients of allogeneic bone marrow. It displays many features of autoimmune diseases such as scleroderma, Sjogren's syndrome, and primary biliary cirrhosis. Although many immune abnormalities have been associated with chronic GVHD, the pathogenesis remains unknown. Spontaneous and rapidly induced chronic GVHD in the rat radiation chimera are clinically and histologically distinct from acute GVHD but very similar to chronic GVHD in humans. Using these multiple models, we have begun making progress towards understanding chronic GVHD. Cellular immunopathology studies with monoclonal antibodies show that the target tissues (skin and liver) have a predominance of helper phenotype cells (W3/25). In contrast with acute GVHD, these tissues have a predominance of nonhelper phenotype T lymphocytes (OX8). Within the skin, the helper phenotype cells with chronic GVHD are within the dermis, whereas with acute GVHD the epidermis is infiltrated with nonhelper (OX8+) cells. By comparing the immune abnormalities of the multiple models of chronic GVHD, we have been able to separate some inconsistently present abnormalities from other abnormalities present in all models. Thus, cutaneous IgM deposits and vasculitis appear to be unnecessary paraphenomena, while thymic medullary changes and nonspecific suppressor cells might be pathogenetically important. Current studies are concentrating on defining the necessary antigen discrepancy and tissue location of antigen disparity, the necessary lymphocyte populations, and the relative roles of immune deficiency versus direct immune injury in producing chronic GVHD. (TT)