PATHOLOGY AND IMMUNOCYTOLOGY OF THE OLIGODENDROCYTE

少突细胞的病理学和免疫细胞学

• 批准号: 3413732
• 负责人: GEORGE R MOORE
• 金额: $ 6.85万
• 依托单位: UNIVERSITY OF BRITISH COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-30 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3413732
• 关键词: autoimmune disorder; cellular immunity; cytokine receptors; disease /disorder model; experimental allergic encephalomyelitis; guinea pigs; histocompatibility antigens; hyperplasia; immunocytochemistry; interleukin 2; laboratory mouse; multiple sclerosis; myelin basic proteins; myelination; myelinopathy; oligodendroglia; receptor binding; tissue /cell culture

In actively demyelinating CNS lesions of multiple sclerosis (MS), proliferation of oligodendrocytes is a common feature and in established lesions, these cells are depleted. The present proposal is designed to test the hypothesis that oligodendrocytes can express interleukin-2 (IL-2) receptors, bind IL-2, express Class I and Class II MHC antigens, and be stimulated to proliferate by myelin breakdown products. Four approaches will be used to study these issues. Firstly, immunoelectron microscopy will be performed on MS lesions to determine if IL-2, IL-2 receptor and Class I and Class II MHC antigens can be demonstrated on the surface of the oligodendrocyte which will also be stained for galactocerebroside (GC) and myelin basic protein (MBP). Similar studies will be carried out on CNS lesions from Strain 13 guinea pigs with chronic relapsing experimental autoimmune encephalomyelitis (EAE), an experimental model which closely resembles MS and which displays extensive remyelination and oligodendroglial hyperplasia after treatment with a MBP-GC mixture. Secondly, to analyze further the factors responsible for the oligodendroglial hyperplasia seen in autoimmune demyelination and MS, oligodendrocyte cultures will be exposed to MBP or fragments of myelin to determine if myelin breakdown products have a mitogenic effect on these cells. Thirdly, to address the controversy of MHC antigen expression by oligobendrocytes, culture oligodendrocytes of various ages from different strains of mice will be studied immunocytochemically for the presence of Class I and Class II MHC at the light and electron microscope levels. Fourthly, a similar study after exposure of the cultures to the lymphokines, IL-2 and interferon-Y, will examine the question of lymphokine induction of MHC on these cells. Thus, these studies should further delineate the role of the oligodendrocyte in the immunopathology of the MS lesion and factors important in the proliferation of this cell, a phenomenon important for remyelination. This information might be relevant to future therapeutic protocols in this disease.

积极地脱髓鞘多发性硬化症（MS）的CNS病变 少突胶质细胞的扩散是一个常见的特征，并且在已建立 病变，这些细胞耗尽。目前的建议旨在 测试少突胶质细胞可以表达白介素2的假设 （IL-2）受体，结合IL-2，Express I类和II类MHC抗原， 并通过髓磷脂分解产品刺激以增殖。四个 方法将用于研究这些问题。首先，免疫电子 显微镜将在MS病变上进行，以确定IL-2，IL-2是否 受体和I类和II类MHC抗原可以在 少突胶质细胞的表面也将染色 半乳脑尿素（GC）和髓磷脂碱性蛋白（MBP）。类似的研究 将在13次豚鼠的CNS病变上进行 慢性复发实验性自身免疫性脑脊髓炎（EAE）， 与MS相似的实验模型，显示 治疗后广泛的再髓和少突胶质增生 与MBP-GC混合物。其次，进一步分析因素 负责自身免疫中看到的寡头增生 脱髓鞘和MS，少突胶质细胞培养物将暴露于MBP或 髓磷脂的片段以确定髓磷脂分解产品是否具有 对这些细胞的有丝分裂作用。第三，解决争议 MHC抗原表达通过少突胶质细胞，培养的少突胶质细胞的抗原表达 将研究来自不同菌株的各种年龄 在I级和II类MHC的情况下进行免疫细胞化学化学。 光和电子显微镜水平。第四，一项类似的研究之后 将培养物暴露于淋巴动物IL-2和Interferon-Y中，将会 检查这些细胞上MHC的淋巴因子诱导问题。 因此，这些研究应进一步描述 MS病变免疫病理学和因素的少突胶质细胞 对于该细胞的扩散很重要，这一现象对 再髓。此信息可能与未来的治疗有关 该疾病的方案。