Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
J Immunol. 2010 Jul 1;185(1):119-25. doi: 10.4049/jimmunol.0902406. Epub 2010 May 28.
Mast cells (MCs) that are well known for their important effector function in IgE-associated immune responses play a key role in innate immune defenses. In this study, we investigate the interaction between MCs and NK cells in vitro and in vivo. We show that mouse bone marrow-derived cultured MCs activated with LPS, polyinosinic-polycytidylic acid, or CpG can stimulate NK cells to secrete increasing concentrations of IFN-gamma. MCs induce a 20-fold increase in IFN-gamma release from NK cells after LPS stimulation. This enhancement of IFN-gamma secretion is cell contact dependent and TNF-alpha independent. Furthermore, we show that this interaction is in part mediated by OX40 ligand on MCs. NK cell-mediated cytotoxicity was not affected by the presence of MCs. Intracellular IFN-gamma levels in splenic NK cells are significantly decreased after i.p. injection of LPS in mast cell-deficient (C57BL/6 Kit(wsh/wsh)) mice in comparison with wild-type mice. In conclusion, our data show for the first time a direct mast cell-dependent NK cell activation. This interaction might play an important role in innate immune defense, as it is dependent on the presence of stimulators relevant in innate immune responses.
肥大细胞（MCs）以其在 IgE 相关免疫反应中的重要效应功能而闻名，在先天免疫防御中发挥着关键作用。在这项研究中，我们研究了 MCs 和 NK 细胞在体外和体内的相互作用。我们表明，用 LPS、聚肌苷酸-聚胞苷酸或 CpG 激活的鼠骨髓来源培养的 MCs 可以刺激 NK 细胞分泌浓度不断增加的 IFN-γ。MCs 诱导 LPS 刺激后 NK 细胞 IFN-γ释放增加 20 倍。这种 IFN-γ分泌的增强依赖于细胞接触，与 TNF-α无关。此外，我们表明这种相互作用部分是由 MCs 上的 OX40 配体介导的。MCs 的存在并不影响 NK 细胞的细胞毒性。与野生型小鼠相比，在缺乏肥大细胞（C57BL/6 Kit(wsh/wsh)）的小鼠中，腹腔内注射 LPS 后，脾 NK 细胞中的细胞内 IFN-γ水平明显降低。总之，我们的数据首次显示了肥大细胞依赖性 NK 细胞的直接激活。这种相互作用可能在先天免疫防御中发挥重要作用，因为它依赖于先天免疫反应中存在的刺激物。
