Bergsteindottir K, Brennan A, Jessen K R, Mirsky R
Department of Anatomy and Developmental Biology, University College of London, England.
Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9054-8. doi: 10.1073/pnas.89.19.9054.
Cells that express major histocompatibility complex (MHC) class II molecules can interact directly with CD4 T lymphocytes and either activate immune reactions or become the targets of T-cell-mediated cytotoxic attack. Using rat optic nerve cultures combined with immunocytochemistry and in situ hybridization, we have shown that oligodendrocytes, the major myelin-forming cells of the central nervous system and the main casualty of the immune attacks associated with multiple sclerosis and experimental allergic encephalomyelitis, can be readily induced to express MHC class II mRNA and surface antigens in vitro by exposure to gamma interferon, provided the glucocorticoid dexamethasone is included in the culture medium. Oligodendrocytes exposed to gamma interferon without dexamethasone fail to express MHC class II molecules, which may account for the failure of previous attempts to induce expression in these cells. In the experiments reported here MHC class II expression can be demonstrated both on galactocerebroside-positive cells and on mature oligodendrocytes that express proteolipid protein. These findings expand possibilities for understanding immune-related oligodendrocyte killing and demyelination in human and experimental demyelinating diseases.
表达主要组织相容性复合体(MHC)II类分子的细胞可直接与CD4 T淋巴细胞相互作用,要么激活免疫反应,要么成为T细胞介导的细胞毒性攻击的靶标。通过将大鼠视神经培养物与免疫细胞化学和原位杂交相结合,我们发现,少突胶质细胞作为中枢神经系统主要的髓鞘形成细胞以及与多发性硬化症和实验性变应性脑脊髓炎相关的免疫攻击的主要受害者,在体外通过暴露于γ干扰素能够很容易地被诱导表达MHC II类mRNA和表面抗原,前提是培养基中含有糖皮质激素地塞米松。未添加地塞米松而暴露于γ干扰素的少突胶质细胞无法表达MHC II类分子,这可能解释了之前在这些细胞中诱导表达失败的原因。在本报告的实验中,MHC II类表达可在半乳糖脑苷脂阳性细胞以及表达蛋白脂质蛋白的成熟少突胶质细胞上得到证实。这些发现为理解人类和实验性脱髓鞘疾病中与免疫相关的少突胶质细胞杀伤和脱髓鞘现象拓展了可能性。