Abstract
BackgroundTight correlation between host circulating CD8+ T cell-mediated immune response and control of viral replication is classical characteristic of long-term HCV infection. CD8+ T cell maturation/activation markers are expected to be associated with viral replication and disease progression in chronic HCV infection. The aim of the present study was to explore novel markers on CD8+ T cells with ability to evaluate HCV viral replication and disease progression.MethodsPBMCs were isolated from 37 chronic HCV-infected patients and 17 healthy controls. Distributed pattern of CD8+ T cells subsets and expression of PD-1, CD38, HLA-DR and CD127 were analyzed by flow cytometry. The correlation between expression of surface markers and HCV viral load or ALT was studied.ResultsDeclined naïve and increased TEMRA CD8+ T subsets were found in HCV-infected individuals compared with healthy controls. Percentage and MFI of PD-1, CD38 and HLA-DR on all CD8+ T cell subsets were higher in HCV-infected patients than healthy controls. In contrast, CD127 expression on CD8+ TCM showed an opposite trend as PD-1, CD38 and HLA-DR did. In chronic HCV infection, MFI of PD-1 on CD8+ TEM (p < 0.0001) and TEMRA (p = 0.0015) was positively correlated with HCV viral load while HLA-DR expression on non-naive CD8+ T cell subsets (p < 0.05) was negatively correlated with HCV viral load.ConclusionPD-1 level on peripheral CD8+ TEM/TEMRA was highly correlated with HCV viral load in chronic HCV-infected patients, which made PD-1 a novel indicator to evaluate HCV replication and disease progression in chronic hepatitis C patients.
Highlights
Tight correlation between host circulating CD8+ T cell-mediated immune response and control of viral replication is classical characteristic of long-term Hepatitis C virus (HCV) infection
Since dysfunctions of viral specific CD8+ T cell immune responses are closely associated with HCV replication [4,5,6], simple and easy-manipulated CD8+ T cell maturation/activation markers which are able to assess viral replication and/or disease progression are desired
Impact of HCV infection on distribution of CD8+ T cell subsets CD8+ T cells can be divided into four subsets according to CD45RA and CD27 expression: naïve (CD45RA+CD27+), TCM (CD45RA-CD27+), TEM (CD45RA-CD27-) and Healthy control (n = 17, F/M = 10/7)
Summary
Tight correlation between host circulating CD8+ T cell-mediated immune response and control of viral replication is classical characteristic of long-term HCV infection. CD8+ T cell maturation/activation markers are expected to be associated with viral replication and disease progression in chronic HCV infection. The aim of the present study was to explore novel markers on CD8+ T cells with ability to evaluate HCV viral replication and disease progression. Since dysfunctions of viral specific CD8+ T cell immune responses are closely associated with HCV replication [4,5,6], simple and easy-manipulated CD8+ T cell maturation/activation markers which are able to assess viral replication and/or disease progression are desired. It has been proposed that unbalanced distribution of circulating CD8+ T cell subsets and impairment of homing capacity and effector function are closely associated with HCV/HIV-1-specific immune tolerance and viral persistence [15,16,17,18,19]
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