Early viraemia clearance during antiviral therapy of chronic hepatitis C improves dendritic cell functions.
Plasma and cellular HCV RNA and core antigen were tested in monocyte-derived DC (MDDC) from chronic hepatitis C patients undergoing treatment with peg-interferon alpha2b/ribavirin. DC allostimulatory capacity, HCV-specific T-cell reactivity and IL-12 production were measured at baseline and treatment week (TW)12. Using DC and autologous CD4(+)T-cells, obtained at baseline and TW12, we performed cross-over experiments to determine the relative role of DC and/or T-cells for impaired immune reactivity to HCV. HCV RNA and HCV core plasma levels had an impact on DC phenotype and allostimulatory capacity. In contrast, HCV genome/core protein, although detectable in DC from some patients had no effect on DC function. Antiviral immunity at TW12 was not improved in patients who remained HCV RNA positive, while early viraemia clearance (TW12) improved antiviral responses. The cross-over experiment revealed that changes in DC, rather than CD4(+)T cells have a major role for enhanced anti-HCV responses.
Pachiadakis
Ioannis
I
Institute of Hepatology, University College London, London, UK. ipachiad@otenet.gr
Chokshi
Shilpa
S
Cooksley
Helen
H
Farmakiotis
Dimitrios
D
Sarrazin
Christoph
C
Zeuzem
Stefan
S
Michalak
Tomasz I
TI
Naoumov
Nikolai V
NV
D000328:Adult; D000956:Antigens, Viral / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D014766:Viremia / Q000188:drug therapy*
D000956:Antigens, Viral; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D018664:Interleukin-12; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b