PMID- 17591020 OWN - NLM STAT- MEDLINE DCOM- 20070806 LR - 20181201 IS - 1359-6535 (Print) IS - 1359-6535 (Linking) VI - 12 IP - 3 DP - 2007 TI - Fate and function of hepatitis-C-virus-specific T-cells during peginterferon-alpha2b therapy for acute hepatitis C. PG - 303-16 AB - 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. FAU - Wiegand, Johannes AU - Wiegand J AD - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany. FAU - Cornberg, Markus AU - Cornberg M FAU - Aslan, Nuray AU - Aslan N FAU - Schlaphoff, Verena AU - Schlaphoff V FAU - Sarrazin, Christoph AU - Sarrazin C FAU - Kubitschke, Anne AU - Kubitschke A FAU - Buggisch, Peter AU - Buggisch P FAU - Ciner, Ayse AU - Ciner A FAU - Jaeckel, Elmar AU - Jaeckel E FAU - Manns, Michael P AU - Manns MP FAU - Wedemeyer, Heiner AU - Wedemeyer H LA - eng PT - Clinical Trial PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - Antivir Ther JT - Antiviral therapy JID - 9815705 RN - 0 (Annexin A5) RN - 0 (Antiviral Agents) RN - 0 (CXCR3 protein, human) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A2 Antigen) RN - 0 (Interferon alpha-2) RN - 0 (Interferon-alpha) RN - 0 (RNA, Viral) RN - 0 (Receptors, CXCR3) RN - 0 (Receptors, Chemokine) RN - 0 (Recombinant Proteins) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - G8RGG88B68 (peginterferon alfa-2b) SB - IM MH - Acute Disease MH - Adult MH - Aged MH - Amino Acid Sequence MH - Annexin A5/metabolism MH - Antiviral Agents/*therapeutic use MH - Binding Sites/genetics/immunology MH - CD4-Positive T-Lymphocytes/immunology/metabolism MH - CD8-Positive T-Lymphocytes/immunology/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Epitopes, T-Lymphocyte/genetics MH - Female MH - Flow Cytometry MH - HLA-A2 Antigen/immunology MH - Hepacivirus/genetics/*immunology MH - Hepatitis C/*drug therapy/immunology/virology MH - Humans MH - Interferon alpha-2 MH - Interferon-alpha/*therapeutic use MH - Lymphocyte Count MH - Male MH - Molecular Sequence Data MH - Polyethylene Glycols MH - RNA, Viral/blood MH - Receptors, CXCR3 MH - Receptors, Chemokine/metabolism MH - Recombinant Proteins MH - Species Specificity MH - Treatment Outcome EDAT- 2007/06/27 09:00 MHDA- 2007/08/07 09:00 CRDT- 2007/06/27 09:00 PHST- 2007/06/27 09:00 [pubmed] PHST- 2007/08/07 09:00 [medline] PHST- 2007/06/27 09:00 [entrez] PST - ppublish SO - Antivir Ther. 2007;12(3):303-16.