Basic—Liver, Pancreas, and Biliary TractAntiviral Intrahepatic T-Cell Responses Can Be Restored by Blocking Programmed Death-1 Pathway in Chronic Hepatitis B
Section snippets
Study Subjects
A total of 42 patients with chronic hepatitis B were enrolled at the Unit of Infectious Diseases and Hepatology of the Azienda Ospedaliero-Universitaria of Parma, Parma, Italy, and at the Department of Clinical Medicine of the University of Bologna, Bologna, Italy. Diagnosis of chronic hepatitis B was based on the detection of alanine aminotransferase (ALT) elevation lasting for more than 6 months, associated with positive hepatitis B surface antigen (HBsAg), antibody to hepatitis B core
Frequency of HBV-Specific CD8 T Cells
To compare the ex vivo frequency and phenotype of HBV-specific CD8 T cells from liver and peripheral blood, 17 HLA-A2- positive patients with chronic hepatitis B were studied with a panel of 6 major histocompatibility complex (MHC) class I tetramers containing frequently detected HBV epitopes (core AA, 18–27; envelope AA, 183–191, AA 335–343, and AA 348–357; and polymerase, AA 575–583 and AA 816–824). Because of limitations in the number of cells available from liver biopsies, staining of LIL
Discussion
Studies in animal models of virus infections show that persistent exposure to high antigen concentrations can affect the antiviral T-cell function by causing different degrees of functional impairment, up to physical T-cell deletion, as a function of the quantity of antigen to which T cells are exposed.29, 30 T-cell exhaustion by this mechanism may play an important role in the pathogenesis of the HBV-specific T-cell hyporesponsiveness of chronic HBV infection because high antigen
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by the VIRGIL EC grant QLK2-CT-2002-00700; by Fondazione Cassa Risparmio di Parma, Parma, Italy; by grant 85/2007, Ricerca Finalizzata, Progetto Ordinario, Ministry of Health, Italy; and by Fondo per gli Investimenti della Ricerca di Base (grant No. RBNE013PMJ); and by the Ministry of Instruction, University and Research, Italy.