Liver Immunology Group, Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Liver Immunology Group, Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia.
J Hepatol. 2015 Oct;63(4):1005-14. doi: 10.1016/j.jhep.2015.05.033. Epub 2015 Jun 20.
The liver is known for its tolerogenic properties. This unique characteristic is associated with persistent infection of the liver by the hepatitis B and C viruses. Improper activation of cellular adaptive immune responses within the liver and immune exhaustion over time both contribute to ineffective cytotoxic T cell responses to liver-expressed antigens in animal models, and likely play a role in incomplete clearance of chronic hepatitis virus infections in humans. However, under some conditions, functional immune responses can be elicited against hepatic antigens, resulting in control of hepatotropic infections. In order to develop improved therapeutics in immune-mediated chronic liver diseases, including viral hepatitis, it is essential to understand how intrahepatic immunity is regulated. This review focuses on CD8 T cell immunity directed towards foreign antigens expressed in the liver, and explores how the liver environment dictates the outcome of intrahepatic CD8 T cell responses. Potential strategies to rescue unresponsive CD8 T cells in the liver are also discussed.
肝脏因其耐受特性而闻名。这种独特的特性与乙型肝炎和丙型肝炎病毒持续感染肝脏有关。肝脏内细胞适应性免疫反应的不当激活以及随着时间的推移免疫衰竭，都导致动物模型中针对肝表达抗原的细胞毒性 T 细胞反应无效，并且可能在人类慢性肝炎病毒感染的不完全清除中发挥作用。然而，在某些情况下，可以针对肝抗原引发功能性免疫反应，从而控制嗜肝感染。为了开发针对免疫介导的慢性肝病（包括病毒性肝炎）的改良疗法，了解肝内免疫是如何调节的至关重要。本综述重点关注针对在肝脏中表达的外来抗原的 CD8 T 细胞免疫，并探讨了肝脏环境如何决定肝内 CD8 T 细胞反应的结果。还讨论了挽救肝脏中无反应性 CD8 T 细胞的潜在策略。
