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在由CD40配体刺激的成熟树突状细胞中,程序性死亡1配体的微调表达对于诱导有效的肿瘤特异性免疫反应至关重要。

Fine-tuned expression of programmed death 1 ligands in mature dendritic cells stimulated by CD40 ligand is critical for the induction of an efficient tumor specific immune response.

作者信息

Gu Tao, Zhu Yi Bei, Chen Cheng, Li Min, Chen Yong Jing, Yu Ge Hua, Ge Yan, Zhou Shi Yong, Zhou Huan, Huang Yong, Qiu Yu Hua, Zhang Xue Guang

机构信息

Medical Biotechnology Institute and Clinical Immunology Laboratory for Jiangsu Province, Soochow University, Suzhou, Jiangsu 215007, China.

出版信息

Cell Mol Immunol. 2008 Feb;5(1):33-9. doi: 10.1038/cmi.2008.4.

Abstract

During maturation, murine myeloid dendritic cells (DCs) upregulated the expressions of CD11c, CD25, CD40, CD80, CD86, MHC II and programmed death 1 ligands 1 and 2 (PD-L1 and PD-L2). Differential expression patterns of PD-L1 and PD-L2 were found when DCs were triggered by CD40 ligand and TNF-alpha. PD-L1 expression was repressed and PD-L2 expression remained unchanged in mature CD40-ligated DCs, whereas TNF-alpha stimulated DCs kept high expression of PD-L1 and significantly enhanced PD-L2 expression on DCs. Proliferations of T lymphocytes stimulated by immature DCs were enhanced by blockade of the PD-1 and PD-1 ligand interaction. But inhibitive effects were found in T lymphocytes stimulated by CD40-ligated DCs. With the fine-tuned expressions of PD-L1 and PD-L2, CD40-ligated DCs could sustain a longer activation period and elicit a more efficient T lymphocyte activation.

摘要

在成熟过程中,小鼠髓样树突状细胞(DCs)上调了CD11c、CD25、CD40、CD80、CD86、MHC II以及程序性死亡1配体1和2(PD-L1和PD-L2)的表达。当DCs由CD40配体和肿瘤坏死因子-α(TNF-α)触发时,发现了PD-L1和PD-L2的差异表达模式。在成熟的CD40连接的DCs中,PD-L1表达受到抑制,而PD-L2表达保持不变,而TNF-α刺激的DCs则保持PD-L1的高表达,并显著增强DCs上PD-L2的表达。通过阻断PD-1和PD-1配体的相互作用,未成熟DCs刺激的T淋巴细胞增殖得到增强。但在CD40连接的DCs刺激的T淋巴细胞中发现了抑制作用。通过对PD-L1和PD-L2的精细调节表达,CD40连接的DCs可以维持更长的激活期,并引发更有效的T淋巴细胞激活。

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