Advertisement

T cell regulation in HBV-related chronic liver disease

  • Carlo Ferrari
    Correspondence
    Corresponding author. Address: Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126 Parma, Italy. Tel.: +39 0521 702762/703622/702056; fax: +39 0521 703857.
    Affiliations
    Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, and Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
    Search for articles by this author
  • Carolina Boni
    Affiliations
    Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, and Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
    Search for articles by this author
  • Marzia Rossi
    Affiliations
    Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, and Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
    Search for articles by this author
  • Andrea Vecchi
    Affiliations
    Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, and Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
    Search for articles by this author
  • Valeria Barili
    Affiliations
    Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, and Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
    Search for articles by this author
  • Diletta Laccabue
    Affiliations
    Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, and Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
    Search for articles by this author
  • Paola Fisicaro
    Affiliations
    Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, and Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
    Search for articles by this author
  • Gabriele Missale
    Affiliations
    Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, and Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
    Search for articles by this author
Published:February 08, 2017DOI:https://doi.org/10.1016/j.jhep.2016.10.002
      HBV-specific T cell dysfunction is believed to play a central role in the pathogenesis of chronic HBV persistence [
      • Bertoletti A.
      • Ferrari C.
      Adaptive immunity in HBV infection.
      ,
      • Rehermann B.
      Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells.
      ]. HBV-specific T cells are more dysfunctional within the liver than in the periphery [
      • Fisicaro P.
      • Valdatta C.
      • Massari M.
      • Loggi E.
      • Ravanetti L.
      • Urbani S.
      • et al.
      Combined blockade of programmed death-1 and activation of CD137 increase responses of human liver T cells against HBV, but not HCV.
      ] as a result of the inhibitory effect of different mechanisms. They are likely to be active simultaneously within the inflamed liver together contributing to T cell functional impairment [
      • Knolle P.A.
      • Thimme R.
      Hepatic immune regulation and its involvement in viral hepatitis infection.
      ,
      • Crispe I.N.
      Immune tolerance in liver disease.
      ]. Some of them have been directly characterized in HBV infection, while others are assumed to be relevant because of their general importance within the liver.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Hepatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bertoletti A.
        • Ferrari C.
        Adaptive immunity in HBV infection.
        J Hepatol. 2016; 64: S71-S83
        • Rehermann B.
        Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells.
        Nat Med. 2013; 19: 859-868
        • Fisicaro P.
        • Valdatta C.
        • Massari M.
        • Loggi E.
        • Ravanetti L.
        • Urbani S.
        • et al.
        Combined blockade of programmed death-1 and activation of CD137 increase responses of human liver T cells against HBV, but not HCV.
        Gastroenterology. 2012; 143: 1576-1585
        • Knolle P.A.
        • Thimme R.
        Hepatic immune regulation and its involvement in viral hepatitis infection.
        Gastroenterology. 2014; 146: 1193-1207
        • Crispe I.N.
        Immune tolerance in liver disease.
        Hepatology. 2014; 60: 2109-2117
        • Wherry E.J.
        • Kurachi M.
        Molecular and cellular insights into T cell exhaustion.
        Nat Rev Immunol. 2015; 15: 486-499
        • Protzer U.
        • Maini M.K.
        • Knolle P.A.
        Living in the liver: hepatic infections.
        Nat Rev Immunol. 2012; 12: 201-213
        • Pallett L.J.
        • Gill U.S.
        • Quaglia A.
        • Sinclair L.V.
        • Jover-Cobos M.
        • Schurich A.
        • et al.
        Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells.
        Nat Med. 2015; 21: 591-600
        • Munn D.H.
        • Mellor A.L.
        Indoleamine 2,3 dioxygenase and metabolic control of immune responses.
        Trends Immunol. 2013; 34: 137-143
        • Oliviero B.
        • Varchetta S.
        • Paudice E.
        • Michelone G.
        • Zaramella M.
        • Mavilio D.
        • et al.
        Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections.
        Gastroenterology. 2009; 137: 1151-1160
        • Peppa D.
        • Gill U.S.
        • Reynolds G.
        • Easom N.J.
        • Pallett L.J.
        • Schurich A.
        • et al.
        Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion.
        J Exp Med. 2013; 210: 99-114
        • Boni C.
        • Lampertico P.
        • Talamona L.
        • Giuberti T.
        • Invernizzi F.
        • Barili V.
        • et al.
        Ferrari C Natural killer cell phenotype modulation and natural killer/T-cell interplay in nucleos(t)ide analogue-treated hepatitis e antigen-negative patients with chronic hepatitis B.
        Hepatology. 2015; 62: 1697-1709
        • Huang L.R.
        • Wohlleber D.
        • Reisinger F.
        • Jenne C.N.
        • Cheng R.L.
        • Abdullah Z.
        • et al.
        Intrahepatic myeloid-cell aggregates enable local proliferation of CD8(+) T cells and successful immunotherapy against chronic viral liver infection.
        Nat Immunol. 2013; 14: 574-583
        • Wong Y.C.
        • Tay S.S.
        • McCaughan G.W.
        • Bowen D.G.
        • Bertolino P.
        Immune outcomes in the liver: Is CD8 T cell fate determined by the environment?.
        J Hepatol. 2015; 63: 1005-1014
        • Guidotti L.G.
        • Inverso D.
        • Sironi L.
        • Di Lucia P.
        • Fioravanti J.
        • Ganzer L.
        • et al.
        Immunosurveillance of the liver by intravascular effector CD8(+) T cells.
        Cell. 2015; 161: 486-500