Department of Hepatobiliary Surgery, Children's Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
Pediatr Res. 2012 Jun;71(6):638-44. doi: 10.1038/pr.2012.17. Epub 2012 Feb 14.
To our knowledge, elucidating the immune pathogenesis of disease, especially characteristic T-cell and natural killer (NK) cell expansions, has not been performed before now. We investigated the role of T lymphocytes and NK lymphocytes in the destruction of extrahepatic bile ducts of patients with biliary atresia.
Lymphocytes from the liver and extrahepatic bile duct remnants of patients with biliary atresia were characterized by immunofluorescence staining, fluorescence-activated cell sorter analysis, and real-time reverse-transcriptase PCR. Cholangiocyte lysis assays were performed to confirm cytotoxicity of activated hepatic NK lymphocytes or CD8(+) cells.
The inflammatory milieu from portal tracts and/or biliary remnants consisted of greater numbers of Kupffer cells, T lymphocytes, and NK lymphocytes in the patients with biliary atresia as compared with the cholestatic and noncholestatic controls. In patients with biliary atresia, expression of NK or CD8+ costimulatory molecules was upregulated as compared with controls. Hepatic NK lymphocytes or CD8(+) cells from patients with biliary atresia were demonstrated to be cytotoxic to the duct epithelium.
Specific immune responses from NK and CD8(+) cells were involved in the injury to the duct epithelium and play a significant role in the phenotype of experimental biliary atresia.
据我们所知，目前尚未阐明疾病的免疫发病机制，特别是特征性 T 细胞和自然杀伤 (NK) 细胞的扩增。我们研究了 T 淋巴细胞和 NK 淋巴细胞在破坏胆道闭锁患者肝外胆管中的作用。
通过免疫荧光染色、荧光激活细胞分选分析和实时逆转录 PCR 对胆道闭锁患者肝和肝外胆管残端的淋巴细胞进行了表征。进行胆管细胞溶解测定以确认活化的肝 NK 淋巴细胞或 CD8+细胞的细胞毒性。
与胆汁淤积和非胆汁淤积对照组相比，胆道闭锁患者的门脉区和/或胆管残端的炎症环境中库普弗细胞、T 淋巴细胞和 NK 淋巴细胞数量增加。与对照组相比，胆道闭锁患者的 NK 或 CD8+共刺激分子表达上调。已经证明胆道闭锁患者的肝 NK 淋巴细胞或 CD8+细胞对胆管上皮具有细胞毒性。
NK 和 CD8+细胞的特异性免疫反应参与了对导管上皮的损伤，并在实验性胆道闭锁的表型中发挥重要作用。
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