Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C.
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.
Erickson
A L
AL
Chiron Corporation, Emeryville, CA 94608.
Houghton
M
M
Choo
Q L
QL
Weiner
A J
AJ
Ralston
R
R
Muchmore
E
E
Walker
C M
CM
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016827:CD8 Antigens / Q000032:analysis; D002460:Cell Line; D002908:Chronic Disease; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D008099:Liver / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016827:CD8 Antigens; D000939:Epitopes; D015395:Histocompatibility Antigens Class I