PD-1 inhibits antiviral immunity at the effector phase in the liver

被引:337
作者
Iwai, YH [1 ]
Terawaki, S [1 ]
Ikegawa, M [1 ]
Okazaki, T [1 ]
Honjo, T [1 ]
机构
[1] Kyoto Univ, Grad Sch Med, Dept Med Chem, Sakyo Ku, Kyoto 6068501, Japan
关键词
T cell; virus; peripheral tolerance; endothelial cell; immuno-inhibition;
D O I
10.1084/jem.20022235
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Unlike naive T cells, effector T cells can be activated by either T cell receptor signal or costimulatory signal alone and therefore the absence of costimulatory molecules on tissue cells cannot explain the tolerance mechanism at the effector phase. Here we report that PD-L1, the ligand for the immunoinhibitory receptor PD-1, was expressed on vascular endothelium in peripheral tissues. Liver nonparenchymal cells including sinusoidal endothelial cells and Kupffer cells constitutively expressed PD-L1 and inhibited proliferation and cell division of activated T cells expressing PD-1. The absence of PD-1 induced proliferation of effector T cells in the adenovirus-infected liver and resulted in rapid clearance of the virus. These results indicate that PD-1 plays an important role in T cell tolerance at the effector phase and the blockade of the PD-1 pathway can augment antiviral immunity.
引用
收藏
页码:39 / 50
页数:12
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