Speeti M, Ståhls A, Meri S, Westermarck E
Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014 Helsinki, Finland.
Vet Immunol Immunopathol. 2003 Nov 15;96(1-2):1-12. doi: 10.1016/s0165-2427(03)00134-x.
Major histocompatibility complex (MHC) class II antigen expression in hepatocytes and its correlation with mononuclear cell infiltration into the liver were studied using immunohistochemical techniques in 38 Dobermans with Doberman hepatitis (DH). Liver biopsy samples were obtained from 18 dogs at the subclinical stage. Autopsy samples were taken from 6 DH dogs euthanized for a reason other than DH, from 14 dogs euthanized because of advanced liver failure and from 6 control Dobermans. Upon examination of the control liver samples, no expression of MHC class II antigens was detected in hepatocytes. By contrast, in 15 of the 18 DH biopsies (83%) and in all 20 DH autopsy liver samples, hepatocytes expressed MHC class II molecules. MHC class II expression was either cytoplasmic or membranous and occurred in conjunction with lymphocyte infiltration. A correlation between the inflammatory reaction and the expression of MHC class II in hepatocytes suggests that the aberrant expression of MHC class II in hepatocytes is induced by cytokines. Hepatocytes presenting a putative MHC class II molecule-associated autoantigen could thus become the target of an immune attack mediated by CD4+ T cells. In addition, corticosteroid treatment was observed to significantly decrease MHC class II expression in DH hepatocytes. Inappropriate MHC class II expression in hepatocytes and mononuclear cell infiltration are suggesting an autoimmune nature for chronic hepatitis in Dobermans.
采用免疫组化技术，对38只患有杜宾犬肝炎（DH）的杜宾犬肝细胞中的主要组织相容性复合体（MHC）II类抗原表达及其与单核细胞浸润肝脏的相关性进行了研究。从18只处于亚临床阶段的犬获取肝活检样本。尸检样本取自6只因非DH相关原因安乐死的DH犬、14只因晚期肝功能衰竭安乐死的犬以及6只对照杜宾犬。检查对照肝脏样本时，未在肝细胞中检测到MHC II类抗原的表达。相比之下，在18份DH活检样本中的15份（83%）以及所有20份DH尸检肝脏样本中，肝细胞表达了MHC II类分子。MHC II类表达为细胞质或膜性，且与淋巴细胞浸润同时出现。肝细胞中炎症反应与MHC II类表达之间的相关性表明，肝细胞中MHC II类的异常表达是由细胞因子诱导的。呈现假定的与MHC II类分子相关自身抗原的肝细胞因此可能成为由CD4 + T细胞介导的免疫攻击的靶标。此外，观察到皮质类固醇治疗可显著降低DH肝细胞中MHC II类的表达。肝细胞中不适当的MHC II类表达和单核细胞浸润提示杜宾犬慢性肝炎具有自身免疫性质。
