Dong Zhongjun, Zhang Jianhong, Sun Rui, Wei Haiming, Tian Zhigang
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei, Anhui 230027, China.
Hepatology. 2007 Jun;45(6):1400-12. doi: 10.1002/hep.21597.
A fraction of HBV carriers have a risk to develop liver cancer. Because liver possesses a strong regeneration capability, surgical resection of cancerous liver or transplantation with healthy liver is an alternate choice for HBV-caused hepatocarcinoma therapy. How HBV infection affects the regeneration of hepatectomized or transplanted liver remains elusive. We report that partial hepatectomy (PHx)-induced liver regeneration was reduced in HBV transgenic (HBV-tg) mice, a model of human HBV infection. PHx markedly triggered natural killer T (NKT) cell accumulation in the hepatectomized livers of HBV-tg mice, simultaneously with enhanced interferon gamma (IFN-gamma) production and CD69 expression on hepatic NKT cells at the early stage of liver regeneration. The impairment of liver regeneration in HBV-tg mice was largely ameliorated by NKT cell depletion, but not by natural killer (NK) cell depletion. Blockage of CD1d-NKT cell interaction considerably alleviated NKT cell activation and their inhibitory effect on regenerating hepatocytes. Neutralization of IFN-gamma enhanced bromodeoxyuridine incorporation in HBV-tg mice after PHx, and IFN-gamma mainly induced hepatocyte cell cycle arrest. Adoptive transfer of NKT cells from regenerating HBV-tg liver, but not from normal mice, could inhibit liver regeneration in recipient mice.
Activated NKT cells negatively regulate liver regeneration of HBV-tg mice in the PHx model.
一部分乙肝病毒携带者有患肝癌的风险。由于肝脏具有强大的再生能力，对癌性肝脏进行手术切除或用健康肝脏进行移植是治疗乙肝病毒所致肝癌的另一种选择。乙肝病毒感染如何影响肝切除或移植肝脏的再生仍不清楚。我们报告，在人类乙肝病毒感染模型乙肝病毒转基因（HBV - tg）小鼠中，部分肝切除术（PHx）诱导的肝脏再生减少。在肝脏再生早期，PHx显著触发了HBV - tg小鼠肝切除肝脏中自然杀伤T（NKT）细胞的聚集，同时肝内NKT细胞上的干扰素γ（IFN - γ）产生增加和CD69表达增强。NKT细胞耗竭在很大程度上改善了HBV - tg小鼠肝脏再生的损伤，但自然杀伤（NK）细胞耗竭则没有。阻断CD1d - NKT细胞相互作用可显著减轻NKT细胞活化及其对再生肝细胞的抑制作用。中和IFN - γ可增强PHx后HBV - tg小鼠中溴脱氧尿苷的掺入，且IFN - γ主要诱导肝细胞细胞周期停滞。从再生的HBV - tg肝脏而非正常小鼠中过继转移NKT细胞，可抑制受体小鼠的肝脏再生。
在PHx模型中，活化的NKT细胞对HBV - tg小鼠的肝脏再生起负向调节作用。
