In vivo clearance of hepatitis C virus nonstructural 3/4A-expressing hepatocytes by DNA vaccine-primed cytotoxic T lymphocytes.
A key question in the development of a therapeutic vaccine against hepatitis C virus (HCV) is whether vaccine-primed T cells enter the liver and eliminate HCV-expressing hepatocytes. In the absence of an infectious small-animal model, we evaluated liver homing of vaccine-primed T cells in mice with transient hepatic transgene expression of the HCV nonstructural 3/4A (NS3/4A) protein. We found that T cells primed by transdermal DNA-based vaccination entered the liver and cleared NS3/4A-expressing hepatocytes in transiently transgenic CD8(+/+) mice but not in CD8(-/-) mice. Hence, peripherally primed NS3/4A-specific CD8(+) T cells home to the liver and clear HCV protein-expressing hepatocytes.
Ahlen
Gustaf
G
Division of Clinical Virology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Nystrom
Jessica
J
Pult
Irmgard
I
Frelin
Lars
L
Hultgren
Catharina
C
Sallberg
Matti
M
D000279:Administration, Cutaneous; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology; D005814:Genes, Viral; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology* / Q000628:therapy / Q000821:virology; D022781:Hepatocytes / Q000276:immunology* / Q000821:virology*; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C455041:NS4A cofactor peptide, Hepatitis C virus; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins