IMMUNOLOGICAL BASIS OF EPILEPSY

这个项目的总体目标是阐明免疫系统的作用， 癫痫的发病机制。在一些癫痫 疾病，具有显著白细胞浸润的炎症已经被 在患者的中枢神经系统中观察到。我们的基本 一种假设是，进入大脑的T细胞在大脑中发挥作用， 在疾病的发生和/或进展中的重要作用， 分泌大量的促炎和神经毒素 介质进入大脑微环境，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， 将详细研究激活的淋巴细胞对 慢性局灶性脑炎（CFE或Rasmussen综合征）， 一种进行性和难治性癫痫， 病理上是局部脑炎症CFE与 进行性神经功能缺损和智力障碍。手术 切除受影响的脑组织是唯一的治疗方法 积极影响癫痫发作频率和疾病进展。 本申请中提出的实验将测试本发明的实施例。 CFE中T和B淋巴细胞特异性和功能。 在第一个目标中，T细胞受体的使用、抗原特异性和 脑梗死患者脑组织和外周血T细胞的特征 将对CFE患者进行研究。我们还将对多态性基因进行分型 在6号染色体的MHC区域，包括HLA II类 决定因素在第二个目标中，我们将分析 脑浸润性T细胞分泌的可溶性信使 他们在死亡期间的功能。在第三个目标中，我们将使用家庭- 用于PCR扩增人IG的特异性前导区引物 CFE脑中的重链可变区基因库。在 此外，将选择单抗原（GluR 3）特异性IG+B细胞 使用抗原包被的磁珠从患者的外周血 以分析免疫球蛋白V区的使用。 这些实验可能会大大阐明 癫痫的免疫反应广泛的合作关系， 团队，获得相关的临床样本，一个极好的研究 环境和暗示性的初步结果，都表明，这一点， 这个项目有很大的成功机会。

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.