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 在接受异基因骨髓移植的患者中常常是致命的并发症。 它 显示出自身免疫性疾病如硬皮病的许多特征， 干燥综合征和原发性胆汁性肝硬化。 虽然许多免疫 异常与慢性GVHD有关， 仍然未知。 放射性嵌合体大鼠自发和快速诱导的慢性GVHD 在临床和组织学上与急性GVHD不同，但非常相似 慢性移植物抗宿主病 使用这些多模型，我们已经开始 在理解慢性GVHD方面取得进展。 蜂窝 单克隆抗体的免疫病理学研究表明， 组织（皮肤和肝脏）具有辅助表型细胞的优势 (W3/25）。 与急性GVHD相比，这些组织具有优势的GVHD。 非辅助表型T淋巴细胞（OX 8）。 在皮肤内， 慢性GVHD的表型细胞位于真皮内，而急性GVHD的表型细胞位于真皮内。 GVHD表皮被非辅助（OX 8+）细胞浸润。 通过比较慢性乙型肝炎多种模型的免疫异常， GVHD，我们已经能够分离出一些不一致的存在 所有模型中存在的其他异常。 因此，在本发明中， 皮肤IgM沉积和血管炎似乎是不必要的 副现象，而胸腺髓质的变化和非特异性抑制 细胞可能是重要的致病因素。目前的研究是 集中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的相对作用 产生慢性GVHD。 （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)