首页    期刊浏览 2024年12月05日 星期四
登录注册

文章基本信息

  • 标题:T-cell activation is enhanced by targeting IL-10 cytokine production in toll-like receptor- stimulated macrophages
  • 本地全文:下载
  • 作者:Ryan M Walk ; Steven T Elliott ; Felix C Blanco
  • 期刊名称:ImmunoTargets and Therapy
  • 电子版ISSN:2253-1556
  • 出版年度:2012
  • 卷号:1
  • 页码:13-23
  • DOI:10.2147/ITT.S32615
  • 出版社:Dove Medical Press Ltd
  • 摘要:Toll-like receptor (TLR) agonists represent potentially useful cancer vaccine adjuvants in their ability to stimulate antigen-presenting cells (APCs) and subsequently amplify the cytotoxic T-cell response. The purpose of this study was to characterize APC responses to TLR activation and to determine the subsequent effect on lymphocyte activation. We exposed murine primary bone marrow-derived macrophages to increasing concentrations of agonists to TLRs 2, 3, 4, and 9. This resulted in a dose-dependent increase in production of not only tumor necrosis factor–alpha (TNF-α), a surrogate marker of the proinflammatory response, but also interleukin 10 (IL-10), a well-described inhibitory cytokine. Importantly, IL-10 secretion was not induced by low concentrations of TLR agonists that readily produced TNF-α. We subsequently stimulated lymphocytes with anti-CD3 antibody in the presence of media from macrophages activated with higher doses of TLR agonists and observed suppression of interferon gamma release. Use of both IL-10 knockout macrophages and IL-10 small-interfering RNA (siRNA) ablated this suppressive effect. Finally, IL-10 siRNA was successfully used to suppress CpG-induced IL-10 production in vivo. We conclude that TLR-mediated APC stimulation can induce a paradoxical inhibitory effect on T-cell activation mediated by IL-10.
  • 关键词:toll-like receptors; innate immunity; IL-10
国家哲学社会科学文献中心版权所有