Abstract
The response of T cells to liver Ags sometimes results in immune tolerance. This has been proposed to result from local, intrahepatic priming, while the expression of the same Ag in liver-draining lymph nodes is believed to result in effective immunity. We tested this model, using an exogenous model Ag expressed only in hepatocytes, due to infection with an adeno-associated virus vector. T cell activation was exclusively intrahepatic, yet in contrast to the predictions of the current model, this resulted in clonal expansion, IFN-gamma synthesis, and cytotoxic effector function. Local activation of naive CD8(+) T cells can therefore cause full CD8(+) T cell activation, and hepatocellular presentation cannot be used to explain the failure of CTL effector function against some liver pathogens such as hepatitis C.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adoptive Transfer
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Animals
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Biomarkers / metabolism
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CD8-Positive T-Lymphocytes / cytology*
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / transplantation
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Cell Differentiation / immunology*
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Cell Line
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Cell Proliferation
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Coculture Techniques
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Cytotoxicity, Immunologic / genetics
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Dependovirus / immunology
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Genetic Vectors
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Green Fluorescent Proteins / immunology*
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Hepatocytes / cytology*
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Hepatocytes / immunology*
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Hyaluronan Receptors / biosynthesis
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L-Selectin / biosynthesis
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Ovalbumin / immunology*
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T-Lymphocytes, Cytotoxic / immunology
Substances
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Biomarkers
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Hyaluronan Receptors
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enhanced green fluorescent protein
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L-Selectin
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Green Fluorescent Proteins
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Ovalbumin