...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin alpha V beta 8
【24h】

Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin alpha V beta 8

机译：Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin alpha V beta 8

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

摘要

Human regulatory T cells (Tregs) suppress other T cells by converting the latent, inactive form of TGF-beta 1 into active TGF-beta 1. In Tregs, TGF-beta 1 activation requires GARP, a transmembrane protein that binds and presents latent TGF-beta 1 on the surface of Tregs stimulated through their T cell receptor. However, GARP is not sufficient because transduction of GARP in non-Treg T cells does not induce active TGF-beta 1 production. RGD-binding integrins were shown to activate TGF-beta 1 in several non-T cell types. Here we show that alpha V beta 8 dimers are present on stimulated human Tregs but not in other T cells, and that antibodies against alpha V or beta 8 subunits block TGF-beta 1 activation in vitro. We also show that alpha V and beta 8 interact with GARP/latent TGF-beta 1 complexes in human Tregs. Finally, a blocking antibody against beta 8 inhibited immunosuppression by human Tregs in a model of xenogeneic graft-vs.-host disease induced by the transfer of human T cells in immunodeficient mice. These results show that TGF-beta 1 activation on the surface of human Tregs implies an interaction between the integrin alpha V beta 8 and GARP/latent TGF-beta 1 complexes. Immunosuppression by human Tregs can be inhibited by antibodies against GARP or against the integrin beta 8 subunit. Such antibodies may prove beneficial against cancer or chronic infections.

著录项

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