Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria.
Institute of Internal Medicine I, Medical University, Vienna, Austria.
Eur J Immunol. 2020 Jun;50(6):880-890. doi: 10.1002/eji.201948222. Epub 2020 Feb 20.
NK cells are innate lymphocytes responsible for lysis of pathogen-infected and transformed cells. One of the major activating receptors required for target cell recognition is the NK group 2D (NKG2D) receptor. Numerous reports show the necessity of NKG2D for effective tumor immune surveillance. Further studies identified NKG2D as a key element allowing tumor immune escape. We here use a mouse model with restricted deletion of NKG2D in mature NKp46 cells (NKG2D ). NKG2D NK cells develop normally, have an unaltered IFN-γ production but kill tumor cell lines expressing NKG2D ligands (NKG2DLs) less efficiently. However, upon long-term stimulation with IL-2, NKG2D-deficient NK cells show increased levels of the lytic molecule perforin. Thus, our findings demonstrate a dual function of NKG2D for NK cell cytotoxicity; while NKG2D is a crucial trigger for cytotoxicity of tumor cells expressing activating ligands it is also capable to limit perforin production in IL-2 activated NK cells.
自然杀伤 (NK) 细胞是固有淋巴细胞，负责裂解病原体感染和转化的细胞。用于靶细胞识别的主要激活受体之一是 NK 组 2D (NKG2D) 受体。许多报道表明 NKG2D 对于有效的肿瘤免疫监视是必需的。进一步的研究表明 NKG2D 是允许肿瘤免疫逃逸的关键因素。我们在这里使用一种在成熟 NKp46 细胞 (NKG2D ) 中限制 NKG2D 缺失的小鼠模型。NKG2D NK 细胞正常发育，IFN-γ 产生未改变，但杀伤表达 NKG2D 配体 (NKG2DLs) 的肿瘤细胞系的效率降低。然而，在长期 IL-2 刺激下，NKG2D 缺陷 NK 细胞显示出更高水平的裂解分子穿孔素。因此，我们的研究结果表明 NKG2D 对 NK 细胞细胞毒性具有双重功能；虽然 NKG2D 是表达激活配体的肿瘤细胞细胞毒性的关键触发因素，但它也能够限制 IL-2 激活的 NK 细胞中穿孔素的产生。
