Fate and function of hepatitis-C-virus-specific T-cells during peginterferon-alpha2b therapy for acute hepatitis C.

Abstract:

BACKGROUND:Strong hepatitis C virus (HCV)-specific T-cell responses are associated with spontaneous clearance of acute hepatitis C. However, recent studies described a decline in HCV-specific CD8+ T-cells during interferon treatment, suggesting that the success of acute HCV therapy might be independent of adaptive immunity. METHODS:T-cell responses of eight human leukocyte antigen (HLA)-A2-positive, acutely infected patients treated with peginterferon-alpha2b were studied by ELISPOT and proliferation assays and flow cytometry analysis using HCV-specific tetramers. RESULTS:HCV-specific T-cells predominately declined during therapy. However, diverse patterns of CD4+ and CD8+ T-cell kinetics were observed. In patients with sustained virological response chemokine receptor 3 (CXCR-3) expression of HCV-specific CD8+ T-cells was upregulated, indicating homing to the liver. Low levels of T-cells remained detectable throughout treatment and follow up. In contrast, T-cells of a relapse patient did not upregulate CXCR-3 but displayed a higher staining for annexin-V, followed by a complete loss of peripheral virus-specific CD8+ T-cells by week 12. CONCLUSIONS:Kinetics of HCV-specific T-cell responses are heterogeneous in interferon-treated patients with acute hepatitis C. The decline of T-cells might be a consequence of both apoptosis and homing. The balance between cell death and regulation of chemokine receptors might lead to different long-term outcomes.

journal_name

Antivir Ther

journal_title

Antiviral therapy

authors

Wiegand J,Cornberg M,Aslan N,Schlaphoff V,Sarrazin C,Kubitschke A,Buggisch P,Ciner A,Jaeckel E,Manns MP,Wedemeyer H

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

303-16

issue

3

eissn

1359-6535

issn

2040-2058

journal_volume

12

pub_type

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