Blocking of interleukin-10 receptor—a novel approach to stimulate T-helper cell type 1 responses to hepatitis C virus

• Published in: Clinical Immunology 2005-10, Vol.117 (1), p.57-64
• Main Authors: Rigopoulou, Eirini I., Abbott, William G.H., Haigh, Philip, Naoumov, Nikolai V.
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Biological and medical sciences; Cell Proliferation - drug effects; Chronic hepatitis C; Cytokines; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hepacivirus - immunology; Hepatitis C - immunology; Hepatitis C virus; Humans; IFN-γ; IL-10; Immunopathology; Immunotherapy; In Vitro Techniques; Interferon-gamma - biosynthesis; Interferon-gamma - drug effects; Interferon-gamma - immunology; Interleukin-10 - biosynthesis; Interleukin-10 - immunology; Male; Medical sciences; Middle Aged; Receptors, Interleukin - antagonists & inhibitors; Receptors, Interleukin - drug effects; Receptors, Interleukin - immunology; Receptors, Interleukin-10; T-cells; Th1 Cells - immunology; Th1 Cells - virology; Th1/Th2 profile
• ISSN: 1521-6616; 1521-7035; 1365-2567
• DOI: 10.1016/j.clim.2005.06.003

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-γ producing T-cells and IFN-γ 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.