title: Immune outcomes in the liver: Is CD8 T cell fate determined by the environment?
abstract: 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.
authors.affiliation: Liver Immunology Group, Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address: m.wong@centenary.org.au.
authors.forename: Yik Chun
authors.initials: YC
authors.lastname: Wong
authors.affiliation: Liver Immunology Group, Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Szun Szun
authors.initials: SS
authors.lastname: Tay
authors.affiliation: Liver Cancer and Injury Group, Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: McCaughan
authors.affiliation: Liver Immunology Group, Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: David G
authors.initials: DG
authors.lastname: Bowen
authors.affiliation: Liver Immunology Group, Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address: p.bertolino@centenary.org.au.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bertolino
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D022781:Hepatocytes / Q000276:immunology / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology
keywords: Antigen load; CD4 T cell help; CD8 T cell exhaustion; Cytotoxic T cells; Immunity; Tolerance; Viral hepatitis