Quantitative analysis of specific Th1/Th2 helper cell responses and IgG subtype antibodies in interferon-alpha-treated patients with chronic hepatitis C.
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.
Hempel
G
G
Department of Internal Medicine, Johannes-Gutenberg University Mainz, Mainz, Germany.
Galle
P R
PR
Löhr
H F
HF
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes; D015331:Cohort Studies; D005260:Female; D018937:Hepatitis C Antibodies / Q000032:analysis* / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016896:Treatment Outcome; D014766:Viremia / Q000188:drug therapy / Q000276:immunology
D018937:Hepatitis C Antibodies; D007074:Immunoglobulin G; D016898:Interferon-alpha; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma