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.

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.

journal_name

J Virol

journal_title

Journal of virology

authors

Radziewicz H,Ibegbu CC,Fernandez ML,Workowski KA,Obideen K,Wehbi M,Hanson HL,Steinberg JP,Masopust D,Wherry EJ,Altman JD,Rouse BT,Freeman GJ,Ahmed R,Grakoui A

doi

10.1128/JVI.02021-06

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

2545-53

issue

6

eissn

0022-538X

issn

1098-5514

pii

JVI.02021-06

journal_volume

81

pub_type

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