• 1
    Ferrari C, Penna A, Bertoletti A, Valli A, Antoni AD, Giuberti T, et al. Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. J Immunol 1990; 145: 34423449.
  • 2
    Maini MK, Boni C, Lee CK, Larrubia JR, Reignat S, Ogg GS, et al. The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med 2000; 191: 12691280.
  • 3
    Boni C, Fisicaro P, Valdatta C, Amadei B, Di Vincenzo P, Giuberti T, et al. Characterization of hepatitis B virus (HBV)-specific T cell dysfunction in chronic HBV infection. J Virol 2007; 81: 42154225.
  • 4
    Chang JJ, Wightman F, Bartholomeusz A, Ayres A, Kent SJ, Sasadeusz J, et al. Reduced hepatitis B virus (HBV)-specific CD4+ T cell responses in human immunodeficiency virus type 1-HBV-coinfected individuals receiving HBV-active antiretroviral therapy. J Virol 2005; 79: 30383051.
  • 5
    Bertoletti A, Maini M, Williams R. Role of hepatitis B virus specific cytotoxic T cells in liver damage and viral control. Antiviral Res 2003; 60: 6166.
  • 6
    Sprengers D, van der Molen RG, Kusters JG, Hansen B, Niesters HG, Schalm SW, et al. Different composition of intrahepatic lymphocytes in the immune-tolerance and immune-clearance phase of chronic hepatitis B. J Med Virol 2006; 78: 561568.
  • 7
    Betts MR, Casazza JP, Patterson BA, Waldrop S, Trigona W, Fu TM, et al. Putative immunodominant human immunodeficiency virus-specific CD8(+) T cell responses cannot be predicted by major histocompatibility complex class I haplotype. J Virol 2000; 74: 91449151.
  • 8
    Woodberry T, Suscovich TJ, Henry LM, Davis JK, Frahm N, Walker BD, et al. Differential targeting and shifts in the immunodominance of Epstein-Barr virus–specific CD8 and CD4 T cell responses during acute and persistent infection. J Infect Dis 2005; 192: 15131524.
  • 9
    Wherry EJ, Blattman JN, Murali-Krishna K, van der Most R, Ahmed R. Viral persistence alters CD8 T cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol 2003; 77: 49114927.
  • 10
    Solomon A, Lane N, Wightman F, Gorry PR, Lewin SR. Enhanced replicative capacity and pathogenicity of HIV-1 isolated from individuals infected with drug-resistant virus and declining CD4+ T cell counts. J Acquir Immune Defic Syndr 2005; 40: 140148.
  • 11
    Maecker HT, Dunn HS, Suni MA, Khatamzas E, Pitcher CJ, Bunde T, et al. Use of overlapping peptide mixtures as antigens for cytokine flow cytometry. J Immunol Methods 2001; 255: 2740.
  • 12
    Betts MR, Casazza JP, Koup RA. Monitoring HIV-specific CD8+ T cell responses by intracellular cytokine production. Immunol Lett 2001; 79: 117125.
  • 13
    Bowden S, Jackson K, Littlejohn M, Locarnini S. Quantification of HBV covalently closed circular DNA from liver tissue by real-time PCR. Methods Mol Med 2004; 95: 4150.
  • 14
    Aye TT, Bartholomeusz A, Shaw T, Bowden S, Breschkin A, McMillan J, et al. Hepatitis B virus polymerase mutations during antiviral therapy in a patient following liver transplantation. J Hepatol 1997; 26: 11481153.
  • 15
    Cooley L, Ayres A, Bartholomeusz A, Lewin S, Crowe S, Mijch A, et al. Prevalence and characterization of lamivudine-resistant hepatitis B virus mutations in HIV-HBV co-infected individuals. AIDS 2003; 17: 16491657.
  • 16
    Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment. J Hepatol 1991; 13: 372374.
  • 17
    Gea-Banacloche JC, Migueles SA, Martino L, Shupert WL, McNeil AC, Sabbaghian MS, et al. Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors. J Immunol 2000; 165: 10821092.
  • 18
    Grabowska AM, Lechner F, Klenerman P, Tighe PJ, Ryder S, Ball JK, et al. Direct ex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection. Eur J Immunol 2001; 31: 23882394.
  • 19
    Spangenberg HC, Viazov S, Kersting N, Neumann-Haefelin C, McKinney D, Roggendorf M, et al. Intrahepatic CD8(+) T cell failure during chronic hepatitis C virus infection. HEPATOLOGY 2005; 42: 828837.
  • 20
    Sprengers D, Molen RG, Kusters JG, Man RA, Niesters HM, Schalm SW, et al. Analysis of intrahepatic HBV-specific cytotoxic T cells during and after acute HBV infection in humans. J Hepatol 2006; 45: 182189.
  • 21
    He XS, Rehermann B, Boisvert J, Mumm J, Maecker HT, Roederer M, et al. Direct functional analysis of epitope-specific CD8+ T cells in peripheral blood. Viral Immunol 2001; 14: 5969.
  • 22
    Milich D, Liang TJ. Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection. HEPATOLOGY 2003; 38: 10751086.
  • 23
    Buer J, Lanoue A, Franzke A, Garcia C, von Boehmer H, Sarukhan A. Interleukin 10 secretion and impaired effector function of major histocompatibility complex class II-restricted T cells anergized in vivo. J Exp Med 1998; 187: 177183.
  • 24
    Abel M, Sene D, Pol S, Bourliere M, Poynard T, Charlotte F, et al. Intrahepatic virus-specific IL-10-producing CD8 T cells prevent liver damage during chronic hepatitis C virus infection. HEPATOLOGY 2006; 44: 16071616.
  • 25
    Bolacchi F, Sinistro A, Ciaprini C, Demin F, Capozzi M, Carducci FC, et al. Increased hepatitis C virus (HCV)-specific CD4+CD25+ regulatory T lymphocytes and reduced HCV-specific CD4+ T cell response in HCV-infected patients with normal versus abnormal alanine aminotransferase levels. Clin Exp Immunol 2006; 144: 188196.
  • 26
    Xu D, Fu J, Jin L, Zhang H, Zhou C, Zou Z, et al. Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. J Immunol 2006; 177: 739747.
  • 27
    Stoop JN, van der Molen RG, Baan CC, van der Laan LJ, Kuipers EJ, Kusters JG, et al. Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. HEPATOLOGY 2005; 41: 771778.
  • 28
    Norris S, Doherty DG, Collins C, McEntee G, Traynor O, Hegarty JE, et al. Natural T cells in the human liver: cytotoxic lymphocytes with dual T cell and natural killer cell phenotype and function are phenotypically heterogenous and include Valpha24-JalphaQ and gammadelta T cell receptor bearing cells. Hum Immunol 1999; 60: 2031.
  • 29
    Takahashi T, Chiba S, Nieda M, Azuma T, Ishihara S, Shibata Y, et al. Cutting edge: analysis of human V alpha 24+CD8+ NK T cells activated by alpha-galactosylceramide-pulsed monocyte-derived dendritic cells. J Immunol 2002; 168: 31403144.
  • 30
    Su F, Schneider RJ. Hepatitis B virus HBx protein sensitizes cells to apoptotic killing by tumor necrosis factor alpha. Proc Natl Acad Sci U S A 1997; 94: 87448749.
  • 31
    Janssen HL, Higuchi H, Abdulkarim A, Gores GJ. Hepatitis B virus enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity by increasing TRAIL-R1/death receptor 4 expression. J Hepatol 2003; 39: 414420.
  • 32
    Saile B, Matthes N, Knittel T, Ramadori G. Transforming growth factor beta and tumor necrosis factor alpha inhibit both apoptosis and proliferation of activated rat hepatic stellate cells. HEPATOLOGY 1999; 30: 196202.
  • 33
    Knittel T, Muller L, Saile B, Ramadori G. Effect of tumour necrosis factor-alpha on proliferation, activation and protein synthesis of rat hepatic stellate cells. J Hepatol 1997; 27: 10671080.
  • 34
    Bertoletti A, D'Elios MM, Boni C, De Carli M, Zignego AL, Durazzo M, et al. Different cytokine profiles of intraphepatic T cells in chronic hepatitis B and hepatitis C virus infections. Gastroenterology 1997; 112: 193199.
  • 35
    McClary H, Koch R, Chisari FV, Guidotti LG. Relative sensitivity of hepatitis B virus and other hepatotropic viruses to the antiviral effects of cytokines. J Virol 2000; 74: 22552264.
  • 36
    Guidotti LG, Ishikawa T, Hobbs MV, Matzke B, Schreiber R, Chisari FV. Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 1996; 4: 2536.
  • 37
    Muhlbauer M, Fleck M, Schutz C, Weiss T, Froh M, Blank C, et al. PD-L1 is induced in hepatocytes by viral infection and by interferon-alpha and -gamma and mediates T cell apoptosis. J Hepatol 2006; 45: 520528.
  • 38
    Radziewicz H, Ibegbu CC, Fernandez ML, Workowski KA, Obideen K, Wehbi M, et al. Liver infiltrating lymphocytes in chronic human HCV infection display an exhausted phenotype with high PD-1 and low CD127 expression. J Virol 2006; 81: 25452553.
  • 39
    Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, et al. PD-1 expression on HIV-specific T cells is associated with T cell exhaustion and disease progression. Nature 2006; 443: 350354.