Blockade of NKG2D on NKT cells prevents hepatitis and the acute response to hepatitis B virus. Vilarinho, S. et al. Proc. Natl Acad. Sci. USA 104, 18187–18192 (2007)
Understanding the immunopathogenesis of liver disease following infection with hepatitis B virus (HBV) is important for the development of new therapeutics. The authors previously established mouse models of primary HBV infection in which non-classical natural killer T (NKT) cells that do not recognize the classical NKT-cell ligand α-galactosylceramide were shown to be sufficient to induce hepatitis. In the present study, the role of the NK- and NKT-cell activating receptor NKG2D in hepatitis was addressed. Surface expression of NKG2D by NK and NKT cells and of the NKG2D ligand RAE1 (retinoic acid early transcript 1) by hepatocytes was modulated during acute infection, and blockade of the NKG2D–ligand interaction prevented acute hepatitis and liver injury. The results support a model in which non-classical NKT cells are activated by HBV infection, leading to the production of cytokines that then activate NK cells.
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