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Am J Pathol. 2011 Nov;179(5):2370-81. doi: 10.1016/j.ajpath.2011.08.004. Epub 2011 Sep 15.

Ineffective CD8(+) T-cell immunity to adeno-associated virus can result in prolonged liver injury and fibrogenesis.

Author information

1
David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, New York, USA. spahnj@wudosis.wustl.edu

Abstract

Chronic viral hepatitis depends on the inability of the T-cell immune response to eradicate antigen. This results in a sustained immune response accompanied by tissue injury and fibrogenesis. We have created a mouse model that reproduces these effects, based on the response of CD8(+) T cells to hepatocellular antigen delivered by an adeno-associated virus (AAV) vector. Ten thousand antigen-specific CD8(+) T cells undergo slow expansion in the liver and can precipitate a subacute inflammatory hepatitis with stellate cell activation and fibrosis. Over time, antigen-specific CD8(+) T cells show signs of exhaustion, including high expression of PD-1, and eventually both inflammation and fibrosis resolve. This model allows the investigation of both chronic liver immunopathology and its resolution.

PMID:
21925469
PMCID:
PMC3204094
DOI:
10.1016/j.ajpath.2011.08.004
[Indexed for MEDLINE]
Free PMC Article
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