Epitopes described in "Delayed induction, not impaired recruitment, of specific CD8⁺ T cells causes the late onset of acute hepatitis C."

Article Authors:Eui-Cheol Shin; Su-Hyung Park; Mary Demino; Michelina Nascimbeni; Kathleen Mihalik; Marian Major; Naga S Veerapu; Theo Heller; Stephen M Feinstone; Charles M Rice; Barbara Rehermann
Article Title:Delayed induction, not impaired recruitment, of specific CD8⁺ T cells causes the late onset of acute hepatitis C.
Reference Detail
Reference ID:1022355
Abstract:BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is characterized by lack of immune-mediated liver injury despite a high level of HCV replication during the incubation phase, which lasts about 8 weeks. We investigated whether this results from delayed recruitment of HCV-specific T cells and whether it facilitates HCV persistence. METHODS: Six chimpanzees were infected with HCV; blood and liver samples were collected for 28 weeks and analyzed for immune cells and chemokines. RESULTS: Two chimpanzees developed self-limited infections, whereas the remaining 4 developed chronic infections. Levels of the chemokines CXCL10, CXCL11, CCL4, and CCL5 increased in blood and liver samples from all chimpanzees within 1 month of HCV infection. Chemokine induction correlated with intrahepatic type I interferon (IFN) responses in vivo and was blocked by neutralizing antibodies against IFN- in vitro. Despite the early-stage induction of chemokines, the intrahepatic lymphocytic infiltrate started to increase no earlier than 8 weeks after HCV infection, when HCV-specific, tetramer-positive CD8(+) T cells appeared in the circulation. The HCV-specific CD8(+) T cells expressed chemokine receptors when they were initially detected in blood samples, so they could be recruited to the liver as soon as they entered the circulation. CONCLUSIONS: Chemokines are induced during early stages of HCV infection, which requires a type I IFN-mediated response. The delayed onset of acute hepatitis does not result from delayed recruitment of HCV-specific T cells, but could instead be related to a primary delay in the induction of HCV-specific T cells. Divergent outcomes occur without evident differences in chemokine induction and T-cell recruitment.
Affiliations:Immunology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
Reference Type:Literature
PubMed ID:21699897
Journal Volume:141
Article Pages:686-95, 695.e1
Journal ISSN:0016-5085
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5555c3e6;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@71b05cce;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@719d12b1;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@7f365cbc;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@4a027be3;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@69139a0a;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5e63c6b;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@4e8897d3;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@69a7c5ec;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5b33f25;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@3af6990f
Article MeSH List:Alanine Transaminase(blood); Animals; Antibodies(immunology); Antigens, CD4(metabolism); Antigens, CD8(metabolism); CD8-Positive T-Lymphocytes(immunology; metabolism; virology); Carcinoma, Hepatocellular(immunology; metabolism); Chemokines(blood; immunology); Hepatitis C(blood; immunology); Intercellular Adhesion Molecule-1(metabolism); Interferon-beta(immunology; metabolism); Interferon-gamma(metabolism); Liver(immunology; metabolism); Liver Neoplasms(immunology; metabolism); Models, Animal; Pan troglodytes; RNA, Messenger(metabolism); RNA, Viral(blood; immunology); Time Factors; Tumor Cells, Cultured; Vascular Cell Adhesion Molecule-1(metabolism); Viral Load
Curation Last Updated:2015-01-18 20:06:07