PD-1 ligands, negative regulators for activation of naive, memory, and recently activated human CD4+ T cells

被引:62
作者
Cai, GF
Karni, A
Oliveira, EML
Weiner, HL
Hafler, DA
Freeman, GJ
机构
[1] Brigham & Womens Hosp, Dept Neurol, Lab Mol Immunol, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
关键词
PD-1; ligand; costimulation; dendritic cells; human T cells; naive T cells; memory T cells; myelin basic protein;
D O I
10.1016/j.cellimm.2004.09.004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We examined the role of the PD-1 pathway on the activation of naive, memory, and recently activated human CD4(+) T cells to test whether they responded differently. PD-1 ligand blockade modestly enhanced the percentage of responding T cells and production of IFN-gamma in a primary response to myelin basic protein (MBP) in normal donors. PD-1 ligand blockade strongly enhanced proliferation and cytokine production by memory or recently activated T cells (tetanus toxoid and MBP). Blockade of PD-L1 alone had more effect than PD-L2, consistent with its higher expression on ex vivo dendritic cells; furthermore, anti-PD-L1 plus anti-PD-L2 resulted in the greatest enhancement. Moreover, PD-L1-Ig inhibited anti-CD3 induced activation of naive, memory, and recently activated CD4+ T cells. Together, our data demonstrated PD-1 functioned as a negative regulatory pathway on naive T cells during a primary response, and more potently, on memory or recently activated T cells during a secondary response. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:89 / 98
页数:10
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