This study aimed to characterise the immune mechanisms relevant to viral clearance in interferon (IFN)-alpha-treated chronic hepatitis C virus (HCV) infection. Proliferative responses of peripheral blood mononuclear cells from sustained complete IFN-alpha therapy responders (n = 8), nonresponders (n = 13), untreated patients (n = 10), and healthy controls (n = 5) were measured retrospectively upon stimulation with recombinant HCV-antigens (core, helicase, NS3, NS4, and NS5) and the secretion of IFN-gamma and interleukins (IL-4, IL-5, IL-10, and IL-12) were tested by ELISA. Furthermore, IFN-gamma as well as IL-10 secreting CD4+ T cells were quantitated by intracellular cytokine staining. Anti-HCV core and NS3-specific IgG subclass antibodies were quantitated in the corresponding patient sera. Sustained therapy responders had more frequent and stronger NS3 and helicase-specific cellular immune responses than nonresponders, untreated HCV patients and healthy controls. Independent from therapy outcome HCV-stimulated T cells in IFN-alpha treated patients secreted preferentially IFN-gamma The Th2 cytokines IL-4 and IL-10 were even decreased in nonresponders, while the IL-12 secretion was not influenced. With respect to the humoral immune response sustained complete responders showed significantly reduced IFN-gamma independent anti-HCV-core and -NS3 IgG1 antibody synthesis. In conclusion, vigorous NS3-specific T-helper cell responses were associated with viral clearance in IFN-alpha recipients; however, the cytokine and antibody analysis argues against a Th1/Th2 imbalance as a major factor that influence the therapy outcome.
Copyright 2001 Wiley-Liss, Inc.