Quantitative analysis of specific Th1/Th2 helper cell responses and IgG subtype antibodies in interferon‐α‐treated patients with chronic hepatitis C

This study aimed to characterise the immune mechanisms relevant to viral clearance in interferon (IFN)‐α‐treated chronic hepatitis C virus (HCV) infection. Proliferative responses of peripheral blood mononuclear cells from sustained complete IFN‐α 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‐γ and interleukins (IL‐4, IL‐5, IL‐10, and IL‐12) were tested by ELISA. Furthermore, IFN‐γ 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‐α treated patients secreted preferentially IFN‐γ 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‐γ 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‐α recipients; however, the cytokine and antibody analysis argues against a Th1/Th2 imbalance as a major factor that influence the therapy outcome. J. Med. Virol. 64:340–349, 2001. © 2001 Wiley‐Liss, Inc.