Interactions between germline-encoded natural killer (NK) cell receptors and their respective ligands on tumorigenic or virus-infected cells determine NK cell cytotoxic activity and/or cytokine secretion. NK cell cytokine responses can be augmented in and can potentially contribute to multiple sclerosis (MS), an inflammatory disease of the central nervous system focused upon the oligodendrocytes (OLs). To investigate mechanisms by which NK cells may contribute to MS pathogenesis, we developed an in vitro human model of OL-NK cell interaction. We found that activated, but not resting human NK cells form conjugates with, and mediate cytotoxicity against, human oligodendrocytes. NK cells, when in conjugate with OLs, rapidly synthesize and polarize IFN-γ toward the OLs. IFN-γ  is capable of reducing myelin oligodendrocyte and myelin associated glycoproteins (MOG and MAG) content. This activity is independent of MHC class-I mediated inhibition via KIR2DL1, but dependent upon the interaction between NK cell-expressed KIR2DL4 and its oligodendrocyte-expressed ligand, HLA-G. NK cells from patients with MS express higher levels of IFN-γ following conjugation to OLs, more actively promote in vitro reduction of MOG and MAG and have higher frequencies of the KIR2DL4 positive population. These data collectively suggest a mechanism by which NK cells can promote pathogenic effects upon OLs.

中文翻译：

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人NK细胞-少突胶质细胞界面上的KIR2DL4-HLAG相互作用调节IFN-γ介导的作用。

种系编码的自然杀伤（NK）细胞受体与致瘤或感染病毒的细胞上各自配体之间的相互作用决定了NK细胞的细胞毒活性和/或细胞因子的分泌。NK细胞的细胞因子反应可以增强，并可能导致多发性硬化症（MS），这是一种集中于少突胶质细胞（OL）的中枢神经系统的炎症性疾病。为了研究NK细胞可能有助于MS发病机理的机制，我们开发了OL-NK细胞相互作用的体外人类模型。我们发现活化的而非静止的人NK细胞与人少突胶质细胞形成结合物，并介导对人少突胶质细胞的细胞毒性。NK细胞与OLs结合时，会迅速合成IFN-γ并使它们极化。IFN-γ能够减少髓磷脂少突胶质细胞和髓磷脂相关糖蛋白（MOG和MAG）的含量。此活性独立于经由KIR2DL1进行的MHC I类介导的抑制，但取决于NK细胞表达的KIR2DL4与少突胶质细胞表达的配体HLA-G之间的相互作用。MS患者的NK细胞与OLs结合后表达更高水平的IFN-γ，更积极地促进MOG和MAG的体外降低，并且KIR2DL4阳性人群的频率更高。这些数据共同表明了NK细胞可以促进对OLs致病作用的机制。MS患者的NK细胞与OLs结合后表达更高水平的IFN-γ，更积极地促进MOG和MAG的体外降低，并且KIR2DL4阳性人群的频率更高。这些数据共同表明了NK细胞可以促进对OLs致病作用的机制。MS患者的NK细胞与OLs结合后表达更高水平的IFN-γ，更积极地促进MOG和MAG的体外降低，并且KIR2DL4阳性人群的频率更高。这些数据共同表明了NK细胞可以促进对OLs致病作用的机制。