IMMUNOLOGICAL BASIS OF EPILEPSY

这个项目的总体目标是阐明免疫的作用。 癫痫发病机制中的反应。在一些癫痫患者中 疾病，炎症与显著的白细胞渗透 在病人的中枢神经系统观察到的。我们的基础 假说是，进入大脑的T细胞发挥着 在疾病的发生和/或发展中的重要作用 分泌大量促炎和神经毒性物质 介体进入大脑微环境，并通过调节 B细胞和巨噬细胞的功能。为了检验我们的假设，我们 将详细研究激活的淋巴细胞对 慢性局灶性脑炎(CFE或拉斯穆森综合征)，a 以进行性和顽固性癫痫为特征 病理上由局灶性脑炎引起。CFE与 进行性神经缺陷和智力障碍。外科手术 切除受影响的脑组织是唯一明确显示的治疗方法。 对癫痫发作频率和疾病进展有积极影响。 本申请中提出的实验将测试 T、B淋巴细胞在CFE中的特异性和功能 在第一个目标中，T细胞受体的使用、抗原特异性和 人脑病灶及外周血中T细胞的特征 将对CFE患者进行研究。我们还将对多态基因进行基因分型 在6号染色体的MHC区域，包括人类白细胞抗原II类 决定因素。在第二个目标中，我们将分析 脑内渗入T细胞分泌的可溶性信使 它们在疾病期间的功能。在第三个目标中，我们将使用家庭- 用于扩增人免疫球蛋白的特异性前导区引物 CFE大脑中的重链可变区基因库。在……里面 此外，将选择单一抗原(GluR3)特异的Ig+B细胞 从患者的外周血中提取抗原包裹的磁珠 以分析免疫球蛋白V区的使用情况。 这些实验可能会相当清楚地揭示出 癫痫的免疫反应。与Skillful建立广泛的协作关系 团队，获得相关临床样本，一项卓越的研究 环境和提示性的初步结果都表明，这 这个项目有很高的成功机会。

The overall goal of this project is to elucidate the role of the immune response in the mechanisms underlying epilepsy. In some epileptic disorders, inflammation with significant leukocytic infiltration has been observed in the patient's central nervous system. Our basic hypothesis is that T cells which have entered the brain play an important role in the initiation and/or progression of diesease by secreting a large number of pro-inflammatory and neurotoxic mediators into the brain microenvironment, and by regulating the function of B cells and macrophages. To examine our hypothesis we will study in detail the contribution of activated lymphocytes to chronic focal encephalitis (CFE or Rasmussen's syndrome), a progressive and intractable form of epilepsy characterized pathologically by focal brain inflammation. CFE is associated with progressive neurologic deficits and intellectual impairment. Surgical removal of the affected brain tissue is the only therapy clearly shown to positively influence seizure frequency and disesase progression. The experiments proposed in the present application will test the specificity and function of T and B lymphocytes in CFE. In the first aim, T cell receptor usage, antigen specificity, and characteristics of T cells in human brain foci and peripheral blood of CFE patients will be studied. We will also genotype polymorphic genes in the MHC region in chromosome 6, including HLA class II determinants. In the second aim, we will analyze the spectrum of soluble messengers secreted by brain infiltrating T cells to asses their function during diesease. In the third aim, we will use family- specific leader-region primers for PCR amplification of the human Ig heavy chain variable-region gene repertoire in the CFE brain. In addition, single antigen (GluR3)-specific Ig+B cells will be selected from patient's peripheral blood using antigen-coated magnetic beads in order to analyze immunoglobulins V region usage. These experiments may shed considerable light on the role of the immune response in epilepsy. Extensive collaborative ties with skillful teams, access to relevant clinical samples, a superb research environment and suggestive preliminary results, all indicate that this project has a high chance of success.