...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Scientific reports. >Treatment of T1D via optimized expansion of antigen-specific Tregs induced by IL-2/anti-IL-2 monoclonal antibody complexes and peptide/MHC tetramers
【24h】

Treatment of T1D via optimized expansion of antigen-specific Tregs induced by IL-2/anti-IL-2 monoclonal antibody complexes and peptide/MHC tetramers

机译：通过IL-2 /抗IL-2单克隆抗体复合物和肽/ MHC四聚体诱导的抗原特异性Tregs的优化膨胀治疗T1d

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Type 1 diabetes can be overcome by regulatory T cells (Treg) in NOD mice yet an efficient method to generate and maintain antigen-specific Treg is difficult to come by. Here, we devised a combination therapy of peptide/MHC tetramers and IL-2/anti-IL-2 monoclonal antibody complexes to generate antigen-specific Treg and maintain them over extended time periods. We first optimized treatment protocols conceived to obtain an improved islet-specific Treg/effector T cell ratio that led to the in vivo expansion and activation of these Treg as well as to an improved suppressor function. Optimized protocols were applied to treatment for testing diabetes prevention in NOD mice as well as in an accelerated T cell transfer model of T1D. The combined treatment led to robust protection against diabetes, and in the NOD model, to a close to complete prevention of insulitis. Treatment was accompanied with increased secretion of IL-10, detectable in total splenocytes and in Foxp3? CD4 T cells. Our data suggest that a dual protection mechanism takes place by the collaboration of Foxp3+ and Foxp3? regulatory cells. We conclude that antigen-specific Treg are an important target to improve current clinical interventions against this disease.
机译：通过NOD小鼠的调节T细胞（Treg）可以克服1型糖尿病，但是难以通过的有效方法产生和维持抗原特异性Treg。这里，我们设计了肽/ MHC四聚体和IL-2 /抗IL-2单克隆抗体复合物的组合治疗，以产生抗原特异性Treg并在延长的时间内保持它们。我们首先进行了优化的治疗方案，以获得改善的胰岛特异性Treg /效应T细胞比，其导致了这些Treg的体内膨胀和激活以及改善的抑制功能。优化的方案应用于治疗Nod小鼠中的糖尿病预防以及T1D的加速T细胞转移模型。合并的治疗导致稳定保护对抗糖尿病，并在NOD模型中，接近完全预防紫外线。治疗伴随着IL-10的分泌增加，可检测在总脾细胞和Foxp3中的可检测？ CD4 T细胞。我们的数据表明，Foxp3 +和Foxp3的协作发生了双保护机制？调节细胞。我们得出结论，抗原特异性Treg是改善对这种疾病的目前临床干预措施的重要目标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号