Blocking of interleukin-10 receptor - a novel approach to stimulate T-helper cell type 1 responses to hepatitis C virus
Blocking of interleukin-10 receptor - a novel approach to stimulate T-helper cell type 1 responses to hepatitis C virus
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DOI：
10.1016/j.clim.2005.06.003
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发表时间：
2005-10-01
影响因子：
8.6
通讯作者：
Naoumov, NV
中科院分区：
文献类型：
--
作者：
Rigopoulou, EI;Abbott, WGH;Naoumov, NV
慢性丙型肝炎病毒（HCV）感染与弱CD4+ t辅助型I反应性和增强的白细胞介素-10对HCV抗原的产生有关。在这里，我们在体外证明了单克隆抗体诱导的IL-10受体（IL-10R）的阻断产生了CD4+ t细胞对HCV反应的有利平衡。将抗IL-10R添加到单核细胞中导致t细胞对HCV核心蛋白、非结构蛋白3和4的增殖反应呈剂量依赖性增加。在竞争实验中，抗il - 10r逆转了IL-10对hcv特异性t细胞增殖的抑制作用。此外，IL-10R的阻断改变了I型抗病毒t细胞反应性的平衡，增加了licv特异性产生ifn - γ的t细胞和ifn - γ分泌的频率。IL-10R阻断对HCV t细胞反应性的影响表明IL-10在抑制抗病毒t细胞反应中起主要作用。阻断IL-10活性可能是提高慢性丙型肝炎抗病毒治疗疗效的有效免疫治疗方法(c) 2005 Elsevier Inc.。版权所有。
Chronic hepatitis C virus (HCV) infection is associated with weak CD4+ T-helper type I 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 I antiviral T-cell reactivity with an increased frequency of liCV-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. (c) 2005 Elsevier Inc. All rights reserved.