Epitopes described in "Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression."

Article Authors:Henry Radziewicz; Chris C Ibegbu; Marina L Fernandez; Kimberly A Workowski; Kamil Obideen; Mohammad Wehbi; Holly L Hanson; James P Steinberg; David Masopust; E John Wherry; John D Altman; Barry T Rouse; Gordon J Freeman; Rafi Ahmed; Arash Grakoui
Article Title:Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression.
Reference Detail
Reference ID:1025959
Abstract:The majority of people infected with hepatitis C virus (HCV) fail to generate or maintain a T-cell response effective for viral clearance. Evidence from murine chronic viral infections shows that expression of the coinhibitory molecule PD-1 predicts CD8+ antiviral T-cell exhaustion and may contribute to inadequate pathogen control. To investigate whether human CD8+ T cells express PD-1 and demonstrate a dysfunctional phenotype during chronic HCV infection, peripheral and intrahepatic HCV-specific CD8+ T cells were examined. We found that in chronic HCV infection, peripheral HCV-specific T cells express high levels of PD-1 and that blockade of the PD-1/PD-L1 interaction led to an enhanced proliferative capacity. Importantly, intrahepatic HCV-specific T cells, in contrast to those in the periphery, express not only high levels of PD-1 but also decreased interleukin-7 receptor alpha (CD127), an exhausted phenotype that was HCV antigen specific and compartmentalized to the liver, the site of viral replication.
Affiliations:Emory University School of Medicine, 954 Gatewood Road N.E., Atlanta, GA 30329, USA.
Reference Type:Literature
PubMed ID:17182670
Journal:J Virol
Journal Volume:81
Article Pages:2545-53
Journal ISSN:1098-5514
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@72bfd569;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@10541b5a;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@1cfba16;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@6cc1fb47;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@33582a19
Article MeSH List:Adult; Aged; Antigens, CD(metabolism); Apoptosis Regulatory Proteins(metabolism); CD8-Positive T-Lymphocytes(immunology; metabolism); Female; Hepacivirus(immunology); Hepatitis C, Chronic(immunology; virology); Humans; Interleukin-7 Receptor alpha Subunit(metabolism); Liver(cytology; immunology); Male; Middle Aged; Programmed Cell Death 1 Receptor; Viral Load
Curation Last Updated:2015-01-18 00:52:17