期刊
CELL REPORTS
卷 23, 期 1, 页码 39-49出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.03.026
关键词
-
类别
资金
- Swiss National Science Foundation [PP00P3_139094, PP00P3_165833]
- European Research Council (ERC) [StG310890]
- ERC [337043-ProtecTC]
- ERC under the European Union's Horizon 2020 research and innovation program [694502]
- Agence Nationale de la Recherche
- Innate Pharma
- MSDAvenir
- Ligue Nationale contre le Cancer (Equipe labelisee La Ligue'')
- Marseille-Immunopole
- Swiss National Science Foundation (SNF) [PP00P3_165833, PP00P3_139094] Funding Source: Swiss National Science Foundation (SNF)
In chronic infection and cancer, T cells acquire a dysfunctional state characterized by the expression of inhibitory receptors. In vitro studies implicated the phosphatase Shp-2 downstream of these receptors, including PD-1. However, whether Shp-2 is responsible in vivo for such dysfunctional responses remains elusive. To address this, we generated T cell-specific Shp-2-deficient mice. These mice did not show differences in controlling chronic viral infections. In this context, Shp-2-deleted CD8(+) T lymphocytes expanded moderately better but were less polyfunctional than control cells. Mice with Shp-2-deficient T cells also showed no significant improvement in controlling immunogenic tumors and responded similarly to controls to alpha-PD-1 treatment. We therefore showed that Shp-2 is dispensable in T cells for globally establishing exhaustion and for PD-1 signaling in vivo. These results reveal the existence of redundant mechanisms downstream of inhibitory receptors and represent the foundation for defining these relevant molecular events.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据