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Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C.

A L Erickson, M Houghton, Q L Choo, A J Weiner, R Ralston, E Muchmore and C M Walker
J Immunol October 15, 1993, 151 (8) 4189-4199;
A L Erickson
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M Houghton
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Q L Choo
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A J Weiner
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R Ralston
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E Muchmore
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C M Walker
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Abstract

Hepatitis C virus (HCV)-specific CTL responses were evaluated in two chimpanzees (Pan troglodytes) during the acute and chronic phases of HCV infection. CD8+ T lymphocytes were isolated from liver tissue homogenates using anti-CD8 antibody-coated magnetic beads and then stimulated with anti-CD3 antibodies, IL-2, and irradiated human PBMC using limiting dilution culture conditions. HCV-specific cytotoxic activity of expanding CD8+ cell lines was assessed against autologous lymphoblastoid cell lines infected with recombinant vaccinia virus vectors encoding HCV Ag. CD8+ T cell lines specific for structural and nonstructural proteins of HCV were established from both animals. Cytolytic activity was blocked with anti-CD8 or anti-class I MHC antibodies, indicating that class I MHC molecules were involved in presentation of viral Ag to the CTL. Overlapping synthetic peptides were used to define a 12 amino acid segment of the nonstructural 3 (NS3) protein recognized by CTL lines from both chimpanzees. Studies with truncated peptides revealed that these CD8+ cell lines were directed against overlapping epitopes presented by distinct class I restriction elements of the chimpanzee MHC complex. CD8+ cell lines with identical specificities for an NS3 epitope were generated from one chronically infected animal at 16 and 28 wk postinfection. These results indicate that virus-specific CTL populations persist in the liver for months, but are unable to resolve chronic HCV infection.

  • Copyright © 1993 by American Association of Immunologists

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The Journal of Immunology
Vol. 151, Issue 8
15 Oct 1993
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Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C.
A L Erickson, M Houghton, Q L Choo, A J Weiner, R Ralston, E Muchmore, C M Walker
The Journal of Immunology October 15, 1993, 151 (8) 4189-4199;

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Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C.
A L Erickson, M Houghton, Q L Choo, A J Weiner, R Ralston, E Muchmore, C M Walker
The Journal of Immunology October 15, 1993, 151 (8) 4189-4199;
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Print ISSN 0022-1767        Online ISSN 1550-6606