CD154, a marker of antigen-specific stimulation of CD4 T cells, is associated with response to treatment in patients with chronic HCV infection.

Abstract

CD4 T-cell function is crucial for the eradication of HCV, and insufficient function is observed in chronic carriers. The monitoring of T-cell responses is complicated by the scarcity of antigen-specific T cells and the relative inefficiency of virus-specific T cells to produce effector cytokines. CD154 is a marker of activation expressed on T cells induced through their T-cell receptor. We analysed CD4 T-cell responses in 72 patients with chronic or resolved HCV infection (23 treatment naïve, 49 treatment experienced, including 16 who had achieved a sustained response). In an additional prospective protocol, 20 of the chronically infected patients were analysed before and after 8-12 weeks of combination therapy with peg-interferon-α and ribavirin. T-cell responses were measured by detecting the expression of CD154 and Th1 cytokines after stimulation with recombinant HCV proteins and were correlated with pretreatment status and outcome of therapy. Broader T-cell responses were observed in treatment naïve than in experienced patients, while the outcome of a preceding therapy regimen did not influence T-cell responses. In the prospective cohort, an on-treatment increase in CD154+ cytokine- T-cell activity was associated with response to treatment, while a decrease was observed in nonresponders. Stronger antigen-independent activity of CD154+ cytokine+ T cells was observed in responders than in nonresponders. Our data indicate that CD154 as a marker of activation of CD4 T cells is a suitable tool for the analysis of T-cell responses in patients with HCV infection.

• Authors: J F Möller, B Möller, B Wiedenmann, T Berg, E Schott
• Journal: Journal of viral hepatitis (J Viral Hepat) Vol. 18 Issue 7 Pg. e341-9 (Jul 2011) ISSN: 1365-2893 [Electronic] England
• PMID: 21692946 (Publication Type: Journal Article)
• Copyright: © 2011 Blackwell Publishing Ltd.

Chemical References

• Antiviral Agents
• Biomarkers
• Interferon-alpha
• Recombinant Proteins
• CD40 Ligand
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2a

Topics

• Adult
• Aged
• Antiviral Agents (therapeutic use)
• Biomarkers
• CD4-Positive T-Lymphocytes (immunology, metabolism, virology)
• CD40 Ligand (biosynthesis)
• Drug Therapy, Combination
• Female
• Hepatitis C, Chronic (drug therapy)
• Humans
• Interferon-alpha (therapeutic use)
• Lymphocyte Activation
• Male
• Middle Aged
• Polyethylene Glycols (therapeutic use)
• Recombinant Proteins (therapeutic use)
• Ribavirin (therapeutic use)
• Treatment Outcome