Hardy C L, Bhathal P S, Snibson K J, Adams T E
Centre for Animal Biotechnology, University of Melbourne, Parkville, Victoria, Australia.
Immunology. 1997 Mar;90(3):412-20. doi: 10.1111/j.1365-2567.1997.00412.x.
Mice expressing an ovine growth hormone-mouse metallothionein promoter fusion gene (METoGH mice) develop chronic hepatitis which becomes progressively more severe over time, hepatocellular adenomas, and eventually carcinoma in the oldest animals. T-lymphocyte expression of activation/memory-associated markers was compared between liver and blood lymphocytes isolated from METoGH and non-transgenic mice at 7, 10 and 12 months of age. The percentage of intrahepatic lymphocytes (IHL) which were CD4+ was markedly diminished in METoGH mice at all times. CD4+ and CD8+ IHL in METoGH mice expressed Ly-6A/6D at increased density, and were CD45RBlo at later time-points. Ly-6C+ and NK1.1+ CD4+ cells, which are common in normal mouse liver, were found at decreased frequency in METoGH livers. Further analysis demonstrated that, as a proportion of total T-cell receptor (TCR) alpha beta cells, NK1.1+ TCR alpha beta int CD4+ cell numbers (NKT cells) were diminished in the livers of METoGH mice. Observations made in METoGH mice support the hypothesis that sustained liver inflammation and hepatocellular injury may be linked to liver cancer. Additionally, it is possible that the relative lack of NKT cells may create an environment permissive for the growth of liver tumours.
表达绵羊生长激素-小鼠金属硫蛋白启动子融合基因的小鼠（METoGH小鼠）会发展为慢性肝炎，且随着时间推移病情会逐渐加重，还会出现肝细胞腺瘤，在最老的动物中最终会发展为肝癌。比较了7、10和12月龄的METoGH小鼠和非转基因小鼠肝脏及血液淋巴细胞中活化/记忆相关标志物的T淋巴细胞表达情况。在所有时间点，METoGH小鼠肝内淋巴细胞（IHL）中CD4⁺细胞的百分比均显著降低。METoGH小鼠的CD4⁺和CD8⁺ IHL表达Ly-6A/6D的密度增加，在后期时间点为CD45RBlo。正常小鼠肝脏中常见的Ly-6C⁺和NK1.1⁺ CD4⁺细胞在METoGH肝脏中的频率降低。进一步分析表明，作为总T细胞受体（TCR）αβ细胞的一部分，METoGH小鼠肝脏中NK1.1⁺ TCRαβint CD4⁺细胞（NKT细胞）数量减少。在METoGH小鼠中的观察结果支持这样的假设，即持续性肝脏炎症和肝细胞损伤可能与肝癌有关。此外，NKT细胞相对缺乏可能会营造一个有利于肝肿瘤生长的环境。
