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

Sílvia Vilarinho, Kouetsu Ogasawara, Stephen Nishimura, Lewis L. Lanier, Jody L. Baron

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)18187-18192
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number46
DOIs
Publication statusPublished - 2007 Nov 13
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Blockade of NKG2D on NKT cells prevents hepatitis and the acute immune response to hepatitis B virus'. Together they form a unique fingerprint.

  • Cite this