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

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

Research output: Contribution to journalArticlepeer-review

349 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2545-2553
Number of pages9
JournalJournal of virology
Volume81
Issue number6
DOIs
StatePublished - Mar 2007

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