Satoh J, Kim S U, Kastrukoff L F
Department of Medicine, University Hospital, University of British Columbia, Vancouver, Canada.
J Neuroimmunol. 1991 Mar;31(3):199-210. doi: 10.1016/0165-5728(91)90041-5.
The cytotoxic activity of killer (K) cells against enriched cultures of bovine oligodendrocytes (BOL) was investigated in multiple sclerosis (MS) and controls. Human K cells mediated cytotoxicity to primary cultures of BOL in the presence of anti-BOL antiserum in all study groups, while BOL were resistant to human natural killer (NK) cells. Cytotoxic activity was significantly reduced in MS when compared to age-matched normal controls but not when compared to other neurologic disease (OND) patients. K cell-mediated lysis of BOL could also be induced with anti-galactocerebroside antibody but not with other antibodies including those specific for OL antigens (myelin basic protein, proteolipid apoprotein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase). Enrichment of the effector population indicated that antibody-dependent cell-mediated cytotoxicity (ADCC) to BOL was mediated by large granular lymphocytes, and the effector population was further characterized by flow cytometry. The effector cells mediating ADCC could be inhibited by protein A of Staphylococcus aureus, and by K562 cells in cold competition assay. These observations indicate that oligodendrocytes are resistant to NK cells but are susceptible to cytolysis mediated by K cells. This may represent a potentially important immune mechanism in the pathogenesis of MS.
在多发性硬化症（MS）患者和对照人群中，研究了杀伤（K）细胞对富集的牛少突胶质细胞（BOL）培养物的细胞毒性活性。在所有研究组中，人K细胞在抗BOL抗血清存在的情况下介导对BOL原代培养物的细胞毒性，而BOL对人自然杀伤（NK）细胞具有抗性。与年龄匹配的正常对照相比，MS患者的细胞毒性活性显著降低，但与其他神经系统疾病（OND）患者相比则无显著差异。抗半乳糖脑苷脂抗体也可诱导K细胞介导的BOL裂解，但其他抗体（包括针对少突胶质细胞抗原的特异性抗体，如髓鞘碱性蛋白、蛋白脂蛋白和2',3'-环核苷酸3'-磷酸二酯酶）则不能。效应细胞群体的富集表明，对BOL的抗体依赖性细胞介导的细胞毒性（ADCC）由大颗粒淋巴细胞介导，并且通过流式细胞术对效应细胞群体进行了进一步表征。介导ADCC的效应细胞可被金黄色葡萄球菌的蛋白A以及冷竞争试验中的K562细胞抑制。这些观察结果表明，少突胶质细胞对NK细胞具有抗性，但易受K细胞介导的细胞溶解作用影响。这可能代表了MS发病机制中一种潜在的重要免疫机制。
