Lauzon Nicole M, Mian Firoz, MacKenzie Randy, Ashkar Ali A
Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, Hamilton, Ont., Canada L8N 3Z5.
Cell Immunol. 2006 Jun;241(2):102-12. doi: 10.1016/j.cellimm.2006.08.004. Epub 2006 Oct 17.
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 51Cr-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.
Toll样受体（TLR）配体是先天性免疫系统的强效诱导剂，其中自然杀伤（NK）细胞和自然杀伤T（NKT）细胞发挥重要作用。我们用已知的TLR配体检测了高度纯化的人NK细胞和/或NKT细胞的直接激活情况。NK/NKT细胞对所有已知的TLR mRNA（TLR1 - 10）呈阳性。TLR2 - 5的配体可诱导纯化的NK细胞产生大量干扰素-γ。然而，TLR9配体未能诱导出显著水平的该细胞因子。从外周血单核细胞（PBMC）中去除NK细胞以证实它们是TLR配体处理后干扰素-γ的主要来源，这导致细胞因子显著减少。使用51Cr标记的K562靶细胞确定TLR配体对NK细胞毒性的直接影响。TLR2 - 5的配体是NK细胞毒性的强效诱导剂，而TLR9配体则不是。我们的结果表明，TLR配体可直接刺激并增强NK细胞细胞因子的产生，并诱导细胞毒性活性。
