MHC MODULATION WITHIN THE BRAIN

对许多领域(艾滋病和其他神经病毒)的临床兴趣 感染、多发性硬化(MS)和其他脱髓鞘 疾病、神经肿瘤、神经移植)引起了人们的关注 对神经抗原的免疫反应，以及它可能是如何 被操纵了。主要组织相容性复合体的作用 在这一背景下，神经组织中的(MHC)是感兴趣的。MHC 产物介导T淋巴细胞和抗原之间的相互作用- 承载细胞。他们的缺席保护了被感染、转化、 损伤并移植T细胞介导的神经组织 监视系统。尽管MHC产品缺乏神经元和 在正常大脑中，神经胶质细胞的表达受到调控。 我们已经开始定义发育和病理 MHC表达较高的情况，以及监管 它可以被操纵的机制。 在这里，我们将继续这项工作，强调与MS的相关性 以及其他脱髓鞘疾病。自身免疫损伤介导的或 T淋巴细胞启动在多发性硬化症的病理过程中起重要作用， MS斑块中可见MHC调制。一种治疗方法 就是试图抑制自身免疫反应。一个困难 就是靶抗原(S)是未知的，也可能不是 每个病人都是一样的。全面的免疫抑制也会 限制神经系统外理想的免疫反应。 了解更多关于MHC调制的潜在生物学知识 大脑可以在两个方面做出贡献：它可以帮助定义 MHC调制在MS中的意义在于 这种疾病的病因学。我们的工作也可能提出这样的方法 MHC的诱导可能在大脑内被选择性地阻止。 (1)我们将定义正常大脑中MHC的基线表达， 以及神经细胞合成MHC的生物合成潜力 产品。(2)我们将检验MHC表达是 在大脑中受到局部控制，通常被积极抑制。 (3)我们将检验神经胶质细胞调节其功能的假设 自己的MHC表达，可能还有神经元和内皮细胞的表达 细胞也是如此。小鼠组织的免疫细胞化学分析 原位、免疫细胞化学和生化分析 将使用人类细胞系。

Clinical interest in many areas (AIDS and other neural viral infections, multiple sclerosis (MS) and other demyelinating diseases, neural tumors, neural transplants) has focused attention on the immune response to neural antigens, and how it may be manipulated. The role of the major histocompatibility complex (MHC) in neural tissue is of interest in this context. MHC products mediate the interaction between T lymphocytes and antigen- bearing cells. Their absence protects infected, transformed, damaged and also transplanted neural tissue from T cell-mediated surveillance. Although MHC products are lacking from neurons and glia in normal brain, their expression is under regulatory control. We have begun to define the developmental and pathological situations in which greater MHC expression is seen, and regulatory mechanisms by which it can be manipulated. Here, we will continue this work, emphasizing the relevance to MS and other demyelinating diseases. Autoimmune damage mediated or initiated by T lymphocytes is important in the pathology of MS, and MHC modulation is seen in MS plaques. One therapeutic approach is to attempt to suppress the autoimmune response. One difficulty is that the target antigen(s) are not known, and they may not be the same in each patient. A general immunosuppression would also limit desirable immune reactions outside the nervous system. Learning more about the underlying biology of MHC modulation in the brain can contribute in two ways: It can help to define the significance of the MHC modulation seen in MS in terms of the etiology of the disease. Our work may also suggest ways in which MHC induction may be prevented selectively within the brain. (1) We will define the baseline MHC expression in normal brain, and the biosynthetic potential of neural cells to synthesize MHC products. (2) We will test the hypothesis that MHC expression is locally controlled in brain, and is normally actively suppressed. (3) We will test the hypothesis that glial cells regulate their own MHC expression, and perhaps that of neurons and endothelial cells as well. Immunocytochemical analysis of mouse tissue in situ, and immunocytochemical and biochemical analysis of murine and human cell lines will be used.