...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >The DC-HIL ligand syndecan-4 is a negative regulator of T-cell allo-reactivity responsible for graft-versus-host disease
【24h】

The DC-HIL ligand syndecan-4 is a negative regulator of T-cell allo-reactivity responsible for graft-versus-host disease

机译：DC-HIL配体syndecan-4是负责移植物抗宿主疾病的T细胞同种反应性的负调节剂

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Acute graft-versus-host disease (GVHD) is the most important cause of mortality after allogeneic haematopoietic stem cell transplantation. Allo-reactive T cells are the major mediators of GVHD and the process is regulated by positive and negative regulators on antigen-presenting cells (APC). Because the significance of negative regulators in GVHD pathogenesis is not fully understood, and having discovered that syndecan-4 (SD-4) on effector T cells mediates the inhibitory function of DC-HIL on APC, we proposed that SD-4 negatively regulates the T-cell response to allo-stimulation in acute GVHD, using SD-4 knockout mice. Although not different from their wild-type counterparts in responsiveness to anti-CD3 stimulation, SD-4-/- T cells lost the capacity to mediate the inhibitory function of DC-HIL and were hyper-reactive to allogeneic APC. Moreover, infusion of SD-4-/- T cells into sub-lethally γ-irradiated allogeneic mice worsened mortality, with hyper-proliferation of infused T cells in recipients. Although there my be little or no involvement of regulatory T cells in this model because SD-4 deletion had no deleterious effect on T-cell-suppressive activity compared with SD-4+/+ regulatory T cells. We conclude that SD-4, as the T-cell ligand of DC-HIL, is a potent inhibitor of allo-reactive T cells responsible for GVHD and a potentially useful target for treating this disease. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
机译：异种造血干细胞移植后，急性移植物抗宿主病（GVHD）是导致死亡的最重要原因。同种反应性T细胞是GVHD的主要介质，该过程由抗原呈递细胞（APC）上的正负调节剂调节。由于尚未完全了解负调节剂在GVHD发病机理中的重要性，并且已发现效应T细胞上的syndecan-4（SD-4）介导了DC-HIL对APC的抑制功能，因此我们建议SD-4负调节该蛋白的表达。使用SD-4基因敲除小鼠，T细胞对急性GVHD中同种异体刺激的反应。尽管SD-4-/-T细胞在抗CD3刺激方面的反应能力与野生型没有区别，但它丧失了介导DC-HIL抑制功能的能力，并且对同种异体APC高度反应。此外，将SD-4-/-T细胞输注至亚致死剂量的γ辐射的同种异体小鼠会使死亡率恶化，受者中注入的T细胞过度增殖。尽管在该模型中我很少或没有参与调节性T细胞，因为与SD-4 + / +调节性T细胞相比，SD-4缺失对T细胞抑制活性没有有害作用。我们得出的结论是，作为DC-HIL的T细胞配体的SD-4是负责GVHD的同种反应性T细胞的有效抑制剂，并且可能是治疗这种疾病的潜在靶标。 2012年发布。本文是美国政府的工作，在美国属于公共领域。

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