Intrahepatic regulation of antiviral T cell responses at initial stages of viral infection

• Liver resident cells play both antigen-presenting functions and immune-inhibitory effects in viral heaptitis.
• Liver kupffer cells are weak antigen presenting cells and induce CD8 T cell exhaustion through IL-10 and PD/1PD-L1 pathway.
• Type 2 and 3 innate lymphoid cells play the different roles in regulating antiviral T cell response in the liver.

It is generally accepted that the appropriate boost of early immune response will control viral replications and limit the immune-mediated pathology in viral hepatitis. However, poor immunity results in viral persistence, chronic inflammation and finally liver cirrhosis and carcinoma. As a peripheral non-lymphoid organ of immune surveillance, the liver continually encounters hundreds of molecules from the blood, including nutrients, toxins and pathogens. In this way, the liver maintains immune tolerance under healthy conditions, but responds quickly to the hepatotropic pathogens during the early stages of an infection. Although our knowledge of liver cell compositions and functions has been improved significantly in recent years, the intrahepatic immune regulation of antiviral T cells at the initial stage is complex and not well elucidated. Here, we summarize the role of liver cell subpopulations in regulating antiviral T cell response at the initial stages of viral infection. A better understanding of early hepatic immune regulation will pave the way for the development of novel therapies and vaccine design for human viral hepatitis.