Blockade of NKG2D on NKT cells prevents hepatitis and the acute immune response to hepatitis B virus

Hepatitis B virus (HBV) is a hepadnavirus that is a major cause of acute and chronic hepatitis in humans. Hepatitis B viral infection itself is noncytopathic, and it is the immune response to the viral antigens that is thought to be responsible for hepatic pathology. Previously, we developed a trans...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2007-11, Vol.104 (46), p.18187-18192
Main Authors: Vilarinho, Sílvia, Ogasawara, Kouetsu, Nishimura, Stephen, Lanier, Lewis L, Baron, Jody L
Format: Article
Language:English
Subjects:
Adoptive transfer
Animals
Antigens
Biological Sciences
Cell Line
Cells
Gene expression
Hepadnavirus
Hepatitis
Hepatitis B
Hepatitis B - prevention & control
Hepatitis B virus
Hepatitis B virus - immunology
Hepatitis B virus - physiology
Hepatocytes
Humans
Infections
Killer Cells, Natural - immunology
Liver
Mice
Mice, Transgenic
Natural killer cells
Natural killer T cells
NK Cell Lectin-Like Receptor Subfamily K
Receptors, Immunologic - antagonists & inhibitors
Receptors, Natural Killer Cell
Rodents
Splenocytes
T lymphocytes
Virus Replication
Viruses
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container_issue 46
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container_title Proceedings of the National Academy of Sciences - PNAS
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Ogasawara, Kouetsu
Nishimura, Stephen
Lanier, Lewis L
Baron, Jody L
description Hepatitis B virus (HBV) is a hepadnavirus that is a major cause of acute and chronic hepatitis in humans. Hepatitis B viral infection itself is noncytopathic, and it is the immune response to the viral antigens that is thought to be responsible for hepatic pathology. Previously, we developed a transgenic mouse model of primary HBV infection and demonstrated that the acute liver injury is mediated by nonclassical natural killer (NK)T cells, which are CD1d-restricted, but nonreactive to α-GalCer. We now demonstrate a role for NKG2D and its ligands in this nonclassical NKT cell-mediated immune response to hepatitis B virus and in the subsequent acute hepatitis that ensues. Surface expression of NKG2D and one of its ligands (retinoic acid early inducible-1 or RAE-1) are modulated in an HBV-dependent manner. Furthermore, blockade of an NKG2D-ligand interaction completely prevents the HBV- and CD1d-dependent, nonclassical NKT cell-mediated acute hepatitis and liver injury. This study has major implications for understanding activation of NKT cells and identifies a potential therapeutic target in treating hepatitis B viral infection.
doi_str_mv 10.1073/pnas.0708968104
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ispartof Proceedings of the National Academy of Sciences - PNAS, 2007-11, Vol.104 (46), p.18187-18192
issn 0027-8424
1091-6490
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source JSTOR Archival Journals; PubMed Central
subjects Adoptive transfer
Animals
Antigens
Biological Sciences
Cell Line
Cells
Gene expression
Hepadnavirus
Hepatitis
Hepatitis B
Hepatitis B - prevention & control
Hepatitis B virus
Hepatitis B virus - immunology
Hepatitis B virus - physiology
Hepatocytes
Humans
Infections
Killer Cells, Natural - immunology
Liver
Mice
Mice, Transgenic
Natural killer cells
Natural killer T cells
NK Cell Lectin-Like Receptor Subfamily K
Receptors, Immunologic - antagonists & inhibitors
Receptors, Natural Killer Cell
Rodents
Splenocytes
T lymphocytes
Virus Replication
Viruses
title Blockade of NKG2D on NKT cells prevents hepatitis and the acute immune response to hepatitis B virus
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