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

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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. © 2011 American Society for Investigative Pathology.

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Spahn, J., Pierce, R. H., & Crispe, I. N. (2011). Ineffective CD8 + T-cell immunity to adeno-associated virus can result in prolonged liver injury and fibrogenesis. American Journal of Pathology, 179(5), 2370–2381. https://doi.org/10.1016/j.ajpath.2011.08.004

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