Osada T, Nagawa H, Kitayama J, Tsuno N H, Ishihara S, Takamizawa M, Shibata Y
Department of Transfusion Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Cell Immunol. 2001 Oct 10;213(1):14-23. doi: 10.1006/cimm.2001.1858.
Dendritic cells (DCs) are essential antigen-presenting cells with a wide variety of functions relating to both adaptive and innate immunity. Recently, interactions of DCs with natural killer (NK) cells and NK1.1-positive T cells have been reported in mice. However, in humans, this interaction is not well understood. Here we report the use of a coculture method to analyze the modulation of NK cell function in antitumor immunity by DCs. We found that peripheral blood DCs (PDCs) enhanced NK cell activity in cytotoxicity assay, even without direct contact between DC and NK cells. In contrast, neither monocyte-derived DCs (MoDCs), nor TNF-alpha-treated MoDCs, stimulated NK lytic activity. Secretion of IL-12 and TNF-alpha into the PDC-NK coculture supernatant was increased. However, blocking antibodies against these cytokines could not completely abolish the upregulation of NK activity, suggesting the presence of other soluble factor(s) that affect DC-NK cell interaction. To summarize, this study demonstrates for the first time the direct activation of human NK cells by DC-NK cell interaction in vitro, suggesting that DCs may have a central role linking the innate and adaptive immune responses. Moreover, in stimulating NK cell function, PDCs appear to have a different potential from MoDCs.
树突状细胞（DCs）是重要的抗原呈递细胞，具有与适应性免疫和先天性免疫相关的多种功能。最近，在小鼠中报道了DCs与自然杀伤（NK）细胞和NK1.1阳性T细胞之间的相互作用。然而，在人类中，这种相互作用尚不清楚。在此，我们报告使用共培养方法来分析DCs在抗肿瘤免疫中对NK细胞功能的调节作用。我们发现，在细胞毒性试验中，外周血DCs（PDCs）增强了NK细胞活性，即使DC和NK细胞之间没有直接接触。相比之下，单核细胞衍生的DCs（MoDCs）以及经TNF-α处理的MoDCs均未刺激NK细胞的裂解活性。PDC-NK共培养上清液中IL-12和TNF-α的分泌增加。然而，针对这些细胞因子的阻断抗体并不能完全消除NK活性的上调，这表明存在其他影响DC-NK细胞相互作用的可溶性因子。总之，本研究首次证明了体外DC-NK细胞相互作用对人NK细胞的直接激活，表明DCs可能在连接先天性免疫和适应性免疫反应中起核心作用。此外，在刺激NK细胞功能方面，PDCs似乎具有与MoDCs不同的潜力。
