BACKGROUND & AIMS: The role of virus-specific T-helper lymphocyte reactivity in determining the therapeutic response in chronic hepatitis C virus (HCV) infection is not fully understood. METHODS: We studied CD4(+) T lymphocyte proliferation together with interferon (IFN)-gamma and interleukin (IL)-10 production from peripheral blood mononuclear cells in response to 4 HCV antigens (core, NS3, NS4, and NS5) in 25 patients with chronic hepatitis C undergoing antiviral therapy with IFN alone or in combination with ribavirin, prospectively, before, during, and after treatment. RESULTS: HCV-specific T-cell reactivity was uncommon at baseline but increased markedly during antiviral therapy, peaking around treatment weeks 4-8. Resolution of hepatitis C viremia was significantly more likely in patients who developed HCV-specific T-cell proliferation with increased IFN-gamma production. The main difference in T-cell reactivity of patients treated with IFN plus ribavirin was a significantly lower production of IL-10, whereas lymphocyte proliferation was similar to that in patients receiving IFN monotherapy. CONCLUSIONS: Treatment-induced control of hepatitis C viremia is associated with the development of HCV-specific T-cell responses with enhanced IFN-gamma and low IL-10 production. The greater efficacy of combination therapy with IFN-alpha plus ribavirin may be related to its ability to suppress HCV-specific IL-10 production.
BACKGROUND & AIMS: The role of virus-specific T-helper lymphocyte reactivity in determining the therapeutic response in chronic hepatitis C virus (HCV) infection is not fully understood. METHODS: We studied CD4(+) T lymphocyte proliferation together with interferon (IFN)-gamma and interleukin (IL)-10 production from peripheral blood mononuclear cells in response to 4 HCV antigens (core, NS3, NS4, and NS5) in 25 patients with chronic hepatitis C undergoing antiviral therapy with IFN alone or in combination with ribavirin, prospectively, before, during, and after treatment. RESULTS:HCV-specific T-cell reactivity was uncommon at baseline but increased markedly during antiviral therapy, peaking around treatment weeks 4-8. Resolution of hepatitis C viremia was significantly more likely in patients who developed HCV-specific T-cell proliferation with increased IFN-gamma production. The main difference in T-cell reactivity of patients treated with IFN plus ribavirin was a significantly lower production of IL-10, whereas lymphocyte proliferation was similar to that in patients receiving IFN monotherapy. CONCLUSIONS: Treatment-induced control of hepatitis C viremia is associated with the development of HCV-specific T-cell responses with enhanced IFN-gamma and low IL-10 production. The greater efficacy of combination therapy with IFN-alpha plus ribavirin may be related to its ability to suppress HCV-specific IL-10 production.
Authors: N H Gruener; F Lechner; M C Jung; H Diepolder; T Gerlach; G Lauer; B Walker; J Sullivan; R Phillips; G R Pape; P Klenerman Journal: J Virol Date: 2001-06 Impact factor: 5.103
Authors: Jason T Blackard; Minhee Kang; Kenneth E Sherman; Margaret James Koziel; Marion G Peters; Raymond T Chung Journal: J Interferon Cytokine Res Date: 2006-11 Impact factor: 2.607
Authors: M Diago; G Castellano; J García-Samaniego; C Pérez; I Fernández; M Romero; O L Iacono; C García-Monzón Journal: Gut Date: 2005-09-08 Impact factor: 23.059
Authors: A Kaser; D Novick; M Rubinstein; B Siegmund; B Enrich; R O Koch; W Vogel; S H Kim; C A Dinarello; H Tilg Journal: Clin Exp Immunol Date: 2002-08 Impact factor: 4.330
Authors: Leland J Yee; KyungAh Im; Abdus S Wahed; Teodorica Bugawan; Jia Li; Shannon L Rhodes; Henry Erlich; Hugo R Rosen; T Jake Liang; Huiying Yang Journal: Antimicrob Agents Chemother Date: 2008-10-13 Impact factor: 5.191
Authors: David E Kaplan; Fusao Ikeda; Yun Li; Nobuhiro Nakamoto; Sutharsan Ganesan; Mary E Valiga; Frederick A Nunes; K Rajender Reddy; Kyong-Mi Chang Journal: J Hepatol Date: 2008-03-07 Impact factor: 25.083