https://scholars.lib.ntu.edu.tw/handle/123456789/545297
標題: | Tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model | 作者: | Chyuan I.-T. Tsai H.-F. Tzeng H.-T. Sung C.-C. Wu C.-S. PEI-JER CHEN PING-NING HSU |
公開日期: | 2015 | 出版社: | Chinese Soc Immunology | 卷: | 12 | 期: | 3 | 起(迄)頁: | 317-325 | 來源出版物: | Cellular and Molecular Immunology | 摘要: | Hepatitis B virus (HBV) reactivation and recurrence are common in patients undergoing immunosuppression therapy. Tumor necrosis factor (TNF) blockage therapy is effective for the treatment of many autoimmune inflammatory diseases. However, the role of TNF-α blockage therapy in the innate and adaptive immune responses against HBV is still not clear. A detailed analysis of HBV infection under TNF-α blockage therapy is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV clearance and T-cell responses were analyzed in a HBV-transfected mouse model under anti-TNF blockage therapy. Our results demonstrated that under TNF-α blockage therapy, HBV viral clearance was impaired with persistent elevated HBV viral load in a dose- and temporal-dependent manner. The impairment of HBV clearance under anti-TNF-α blockage therapy occurred at early time points after HBV infection. In addition, TNF-α blockade maintained a higher serum HBV viral load and increased the number of intrahepatic programmed cell death (PD)-1 high CD127 low exhausted T cells. Furthermore, TNF-α blockade abolished Toll-like receptor 9 (TLR9) ligand-induced facilitation of HBV viral clearance. Taken together, TNF-α blockade impairs HBV clearance and enhances viral load, and these effects depend on early administration after HBV infection. Our results here demonstrate that early TNF-α blockade reduces viral clearance and persistently maintains elevated HBV viral load in a mouse model, suggesting that HBV may reactivate during therapy with TNF-α-blocking agents. ? 2015 CSI and USTC. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984593047&doi=10.1038%2fcmi.2015.01&partnerID=40&md5=248b4ce35cee8849c87ff9bfbe0c6e61 https://scholars.lib.ntu.edu.tw/handle/123456789/545297 |
ISSN: | 1672-7681 | DOI: | 10.1038/cmi.2015.01 | SDG/關鍵字: | etanercept; interleukin 7 receptor; programmed death 1 receptor; blocking antibody; interleukin 7 receptor alpha; Pdcd1 protein, mouse; programmed death 1 receptor; Tlr9 protein, mouse; toll like receptor 9; tumor necrosis factor; animal cell; animal experiment; animal model; animal tissue; antigen expression; Article; cellular immunity; controlled study; dose response; early intervention; hepatitis B; Hepatitis B virus; in vivo study; male; mouse; nonhuman; single drug dose; T lymphocyte; viral clearance; virus load; virus reactivation; animal; Bagg albino mouse; C57BL mouse; cell survival; disease model; drug effects; genetics; Hepacivirus; hepatitis B; human; immunology; immunosuppressive treatment; immunotherapy; knockout mouse; metabolism; pathology; virology; virus activation; Hepatitis B virus; Animals; Antibodies, Blocking; Cell Survival; Disease Models, Animal; Hepacivirus; Hepatitis B; Humans; Immunosuppression; Immunotherapy; Interleukin-7 Receptor alpha Subunit; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Programmed Cell Death 1 Receptor; T-Lymphocytes; Toll-Like Receptor 9; Tumor Necrosis Factor-alpha; Viral Load; Virus Activation |
顯示於: | 醫學系 |
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