Antigen-specific cytokine response to hepatitis C virus core epitopes in HIV/hepatitis C virus-coinfected patients

Objective: Epidemiological data indicate that hepatitis C virus (HCV) infec tion runs a more rapid and severe course of disease in HIV-coinfected patie nts, probably because of an altered immune response. Design: We investigated whether HCV-specific cytokine responses are affecte d by HIV coinfection. Methods: Using triple colour flow cytometry on peripheral blood lymphocytes after stimulation with the four major immunodominant HCV core T cell epito pes, CT1-CT4, we determined intracytoplasmic production of IFN-gamma, IL-2, IL-4, IL-10 and CD30 expression, a putative surrogate marker of type 2 cel ls. Fifteen patients with asymptomatic HIV/HCV coinfection (group A), 15 pa tients with chronic HCV infection (group B) and 10 HIV-infected patients wi thout hepatitis C (group C) were included in the study. Results: In group A, HCV antigens induced significantly higher IL-2 and IFN -gamma production than groups B and C (P < 0.05). Groups A and B showed a s imilar induction of CD30, which was significantly higher than in group C (P < 0.001). Remarkably, in group A HCV antigens induced IL-4 production in a ddition to IL-10 and IFN-gamma in the CD30 subset, whereas in groups B and C no IL-4 induction was observed in this T cell subset (P < 0.002). Conclusion: Our data suggest that asymptomatic HIV coinfection importantly alters the HCV-specific cytokine response towards a greater production of p roinflammatory type 1 cytokines. Moreover, the antiviral activity of type 1 cytokines may be modified by an increased production of type 2 cytokines i n the CD30 subset. The altered cytokine pattern may contribute to the adver se natural course of hepatitis C in HIV coinfection. (C) 1999 Lippincott Wi lliams & Wilkins.