Blocking of interleukin-10 receptor--a novel approach to stimulate T-helper cell type 1 responses to hepatitis C virus.
Chronic hepatitis C virus (HCV) infection is associated with weak CD4+ T-helper type 1 reactivity and enhanced interleukin-10 production to HCV antigens. Here we demonstrate in vitro that monoclonal antibody-induced blockade of IL-10 receptor (IL-10R) generates a favorable balance of CD4+ T-cell responses to HCV. The addition of anti-IL-10R to mononuclear cells leads to a dose-dependent increase of T-cell proliferative response to HCV core, non-structural proteins 3 and 4. In competition experiments, anti-IL-10R reversed the inhibitory effect of IL-10 on HCV-specific T-cell proliferation. Furthermore, the blockade of IL-10R altered the balance towards type 1 antiviral T-cell reactivity with an increased frequency of HCV-specific IFN-gamma producing T-cells and IFN-gamma secretion. The impact of IL-10R blockade on T-cell reactivity to HCV demonstrates the major role of IL-10 in suppressing antiviral T-cell responses. Blocking IL-10 activity may be a useful immunotherapy approach to enhance the efficacy of antiviral treatment in chronic hepatitis C.
Rigopoulou
Eirini I
EI
Institute of Hepatology, University College London, UK.
Abbott
William G H
WG
Haigh
Philip
P
Naoumov
Nikolai V
NV
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000276:immunology*; D053701:Receptors, Interleukin-10; D018417:Th1 Cells / Q000276:immunology* / Q000821:virology*
D000911:Antibodies, Monoclonal; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D007371:Interferon-gamma