MHC MODULATION WITHIN THE BRAIN

临床兴趣在许多领域（艾滋病和其他神经病毒 感染、多发性硬化症（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，以及它是如何 被操纵了 主要组织相容性复合体的作用 (MHC)在神经组织中的作用是很有意义的。 MHC 产物介导T淋巴细胞和抗原之间的相互作用， 产生细胞。 它们的缺失保护了被感染的，被转化的， 受损的和移植的T细胞介导的神经组织 监视 虽然MHC产物缺乏神经元和 在正常脑中，它们的表达受到调控。 我们已经开始定义发展和病理 在这种情况下，可以看到更多的MHC表达， 它可以被操纵的机制。 在这里，我们将继续这项工作，强调MS的相关性 和其他脱髓鞘疾病。 自身免疫损伤介导或 由T淋巴细胞引发的免疫应答在MS的病理学中是重要的， 并且在MS斑块中观察到MHC调节。 一种治疗方法 就是试图抑制自身免疫反应 一个困难 靶抗原是未知的，并且它们可能不是已知的。 每个病人都一样。 一般的免疫抑制也会 限制神经系统外的理想免疫反应。 了解更多关于MHC调节的基础生物学， 大脑可以通过两种方式做出贡献：它可以帮助定义 在MS中观察到的MHC调节的重要性， 疾病的病因。我们的工作也可能提出一些方法， MHC诱导可以在脑内选择性地被阻止。 (1)我们将定义正常大脑中MHC表达的基线， 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 在大脑中局部控制，并且通常被主动抑制。 (3)我们将检验神经胶质细胞调节其 自身的MHC表达，也许还有神经元和内皮细胞的MHC表达， 细胞也是。 免疫细胞化学分析小鼠组织中 原位、免疫细胞化学和生物化学分析， 将使用人细胞系。

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.