...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>International immunopharmacology >Generation of human regulatory T cells de novo with suppressive function prevent xenogeneic graft versus host disease.
【24h】

Generation of human regulatory T cells de novo with suppressive function prevent xenogeneic graft versus host disease.

机译：从头产生具有抑制功能的人类调节性T细胞可防止异种移植物抗宿主疾病。

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

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

摘要

Treatment with rapamycin (RAPA) favorably affects regulatory T cells (Treg) in vivo, and RAPA induces the de novo expression of FOXP3 in murine alloantigen-specific T cells. Whether RAPA acts independently or with transforming growth factor beta (TGF-beta) to produce ex vivo-induced Treg generation is unknown. Naive CD4(+) T cells isolated from peripheral blood mononuclear cells were stimulated with anti-CD3/CD28 coated beads in the presence of IL-2 for 5 to 7 days. Ten ng/ml of TGF-beta (1 to 100 ng/mL RAPA) was added to some of the cultures. The phenotypes were analyzed with flow cytometry. The conditioned cells were cocultured with CFSE-labeled T cells in different ratios for 5 days. CFSE dilution indicating T response cell proliferation was analyzed by flow cytometry. Xenogeneic graft-versus-host disease (x-GVHD) was induced by transplanting human peripheral blood mononuclear cells into RAG2(-/-) gammac(-/-) mice exposed to total body irradiation, and various factors in the subjects were subsequently compared. CD4 cells induced by rapamycin and TGF-beta (CD4(RAPA/TGF-beta)) expressed the natural Treg phenotypes and trafficking receptors, and no significant cytotoxicity was observed. CD4(RAPA/TGF-beta) was anergic and demonstrated potent suppressive activity in vitro. Although the transfer of human peripheral blood mononuclear cells into RAG2(-/-) gammac(-/-) mice caused x-GVHD, the cotransfer of CD4(RAPA/TGF-beta) decreased human cell engraftment and extended survival in mice. RAPA plus TGF-beta induces human naive T cells to become suppressor cells, a novel strategy for treating human autoimmune diseases and preventing allograft rejection.
机译：雷帕霉素（RAPA）的治疗有利地影响体内的调节性T细胞（Treg），并且RAPA诱导鼠异源抗原特异性T细胞中FOXP3的从头表达。 RAPA是独立起作用还是与转化生长因子β（TGF-beta）共同产生离体诱导的Treg产生尚不清楚。在IL-2存在下，用抗CD3 / CD28包被的小珠刺激从外周血单核细胞分离的幼稚CD4（+）T细胞刺激5至7天。向某些培养物中添加10 ng / ml的TGF-β（1至100 ng / mL的RAPA）。用流式细胞仪分析表型。将条件化的细胞与CFSE标记的T细胞以不同比例共培养5天。通过流式细胞术分析表明T反应细胞增殖的CFSE稀释液。通过将人外周血单核细胞移植到暴露于全身照射的RAG2（-/-）gammac（-/-）小鼠中，诱发异种移植物抗宿主病（x-GVHD），随后比较了受试者的各种因素。雷帕霉素和TGF-β（CD4（RAPA /TGF-β））诱导的CD4细胞表达天然Treg表型和运输受体，未观察到明显的细胞毒性。 CD4（RAPA / TGF-beta）具有镇痛作用，并在体外具有较强的抑制作用。虽然人类外周血单核细胞转移到RAG2（-/-）gammac（-/-）小鼠中引起了x-GVHD，但CD4（RAPA / TGF-beta）的共转移减少了人类细胞的植入并延长了小鼠的生存期。 RAPA加TGF-β诱导人类幼稚T细胞成为抑制细胞，这是一种治疗人类自身免疫性疾病和预防同种异体移植排斥的新策略。

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