Nonomura A, Kono N, Minato H, Nakanuma Y
Pathology Section, Kanazawa University Hospital, Ishikawa, Japan.
Pathol Int. 1998 Jun;48(6):421-7. doi: 10.1111/j.1440-1827.1998.tb03927.x.
Experimental graft-versus-host disease (GVHD) across minor histocompatibility antigens was developed by injecting spleen and bone marrow cells (9:1) of congenic B10.D2 mice into sublethally irradiated BALB/c mice, and the histologic features of the liver were studied for up to 14 months after transplantation. Both intrahepatic and extrahepatic bile ducts were severely involved in the GVHD process and showed features of non-suppurative cholangitis. Inflammatory cells, mainly lymphocytes, abutted the bile ducts and infiltrated into the duct epithelial layer together with a variety of degenerative changes in the epithelial cells. The peak inflammatory activity occurred about 2-3 weeks after transplantation. Thereafter, the inflammatory cell infiltration around the bile ducts and in the bile duct epithelial layer gradually became reduced in severity, although the infiltration persisted during the entire 14 month observation period. Periductal and duct wall fibroplasia began about 1 week after transplantation and gradually progressed. After 2-3 months post-transplantation, distinct ductal and periductal fibrosis of both intrahepatic and extrahepatic bile ducts was observed. This histologic feature resembled that of primary sclerosing cholangitis (PSC). These results suggest that PSC lesions might develop as a result of chronic cellular immunologic mechanisms in GVHD across minor histocompatibility barriers.
通过将同基因B10.D2小鼠的脾细胞和骨髓细胞（9:1）注射到亚致死剂量照射的BALB/c小鼠体内，建立了跨次要组织相容性抗原的实验性移植物抗宿主病（GVHD），并在移植后长达14个月的时间内研究了肝脏的组织学特征。肝内和肝外胆管在GVHD过程中均受到严重影响，并表现出非化脓性胆管炎的特征。炎症细胞主要是淋巴细胞，紧靠胆管并与上皮细胞的各种退行性变化一起浸润到胆管上皮层。炎症活动高峰出现在移植后约2-3周。此后，胆管周围和胆管上皮层的炎症细胞浸润程度逐渐减轻，尽管在整个14个月的观察期内浸润持续存在。移植后约1周开始出现导管周围和管壁纤维增生，并逐渐进展。移植后2-3个月，观察到肝内和肝外胆管明显的导管和导管周围纤维化。这种组织学特征类似于原发性硬化性胆管炎（PSC）。这些结果表明，PSC病变可能是由于跨次要组织相容性屏障的GVHD中的慢性细胞免疫机制所致。
