The direct effects of Toll-like receptor ligands on human NK cell cytokine production and cytotoxicity

The direct effects of Toll-like receptor ligands on human NK cell cytokine production and cytotoxicity
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DOI:
10.1016/j.cellimm.2006.08.004
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发表时间:
2006-06-01
影响因子:
4.3
通讯作者:
Ashkar, Ali A.
Ashkar, Ali A.
中科院分区:
医学4区
文献类型:
--
作者:
Lauzon, Nicole M.;Mian, Firoz;Ashkar, Ali A.

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Toll样受体(TLR)配体是天然免疫系统的有效诱导剂,其中NK和NKT细胞发挥重要作用。我们研究了用已知TLR配体直接活化高度纯化的人NK和/或NKT细胞。NK/NKT细胞对所有已知的TLR mRNA(TLR 1 -10)呈阳性。TLR 2 -5的配体通过纯化的NK细胞诱导显著量的IFN-γ的产生。然而,TLR 9配体未能诱导显著水平的细胞因子。从PBMC中耗尽NK细胞以确认它们是用TLR配体处理后IFN-γ的主要来源,这导致细胞因子的显著减少。TLR配体对NK细胞毒性的直接作用使用SCr标记的K562靶细胞测定。TLR 2 -5的配体是NK细胞毒性的有效诱导剂,TLR 9配体不是。我们的研究结果表明,TLR配体可以直接刺激和增强NK细胞细胞因子的产生,并诱导细胞毒活性。(c)2006年爱思唯尔公司All rights reserved.
Toll-like receptor (TLR) ligands are potent inducers of the innate immune system, of which NK and NKT cells play an important role. We examined the direct activation of highly purified human NK and/or NKT cells with known TLR ligands. NK/NKT cells were positive for all known TLR mRNA (TLR1-10). Ligands for TLR2-5 induced production of significant amounts of IFN-gamma by purified NK cells. However, a TLR9 ligand failed to induce significant levels of the cytokine. NK cells were depleted from PBMCs to confirm that they were the main source of IFN-gamma following treatment with TLR ligands, which resulted in a significant decrease in cytokines. The direct effects of TLR ligands on NK cytotoxicity were determined using SCr-labeled K562 target cells. Ligands for TLR2-5 were potent inducers of NK cell cytotoxicity, a TLR9 ligand was not. Our results suggest that TLR ligands can directly stimulate and enhance NK cell cytokine production and induce cytotoxic activities. (c) 2006 Elsevier Inc. All rights reserved.