Hepatitis B virus (HBV) infection is a major cause of hepatic inflammation. Successful HBV clearance in patients is associated with sustained viral control by effector T cells. Compared with acute hepatitis B, chronic HBV infection is associated with the depletion of
T cells, resulting in weak or absent virusspecific T cells reactivity, which is described as ‘exhaustion’. This exhaustion is characterized by impaired cytokine production and sustained expression of multiple coinhibitory molecules. Cytotoxic T lymphocyteassociated antigen4
(CTLA4) is one of many coinhibitory molecules that can attenuate T cell activation by inhibiting costimulation and transmitting inhibitory signals to T cells. Persistent HBV infection results in the upregulation of CTLA4 on hepatic CD8+ T cells. This prompts CD8+ T cell
apoptosis, and the activation of cytotoxic T lymphocytes is blocked. Similar to CD8+ T cells, CD4+ T helper (Th) cell proliferation is hindered following CTLA4 upregulation. In addition, the differentiation of CD4+ Th is polarized toward the Th2/peripherallyinducible T regulatory cell
types, increasing the levels of antiinflammatory cytokines. Conversely, the activation of proinflammatory cells (Th1 and follicular helper T) is blocked, and the levels of proinflammatory cytokines decline. This review summarizes the current literature relevant to T cell exhaustion in
patients with HBVrelated chronic hepatitis, and discusses the roles of CTLA4 in T cell exhaustion.
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Document Type: Research Article
Department of Liver Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, P.R. China
Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, TX 79106, USA
Publication date: January 1, 2018
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The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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