KILLER T CELL ACTIVITY IN PARANEOPLASTIC NEUROLOGIC SYNDROME

副肿瘤神经综合征中的杀伤性 T 细胞活性

• 批准号: 6277121
• 负责人: ROBERT B DARNELL
• 金额: $ 5.84万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277121
• 关键词: autoimmune disorder; cellular immunity; clinical research; cytotoxic T lymphocyte; human subject; human tissue; neoplasm /cancer immunology; nervous system disorder; tumor antigens

The paraneoplastic neurologic diseases (PND's) are a diverse group of neurological disorders arising in the setting of cancer that are believed to have an immunological basis. It is believed that the disorders are triggered when systemic tumors express proteins normally made only in neurons, leading to effective anti-tumor immunity and autoimmune neuronal degeneration. We have utilized high titer antibodies present in the serum and CSF of PND patients to classify the disorders and identify the target antigens. However, treatment protocols that reduce antibody titers show no clinical response, and passive transfer of antibody or induction of antibody responses in animals do not reproduce the disorders. We propose to explore the contribution of B and T cells to the clinical disorder; in particular, we suspect and will specifically search for a previously unidentified T cell component to the disease. In preliminary studies, we have been able to find evidence for a specific cytotoxic T cell immune response in the serum and spinal fluid of several PND patients. We will attempt to modify the autoimmune response in order to improve clinical outcome, monitoring both clinical and immunological parameters.

副肿瘤性神经系统疾病(PND‘s)是一组不同的 在癌症的背景下出现的神经障碍被认为是 才有了免疫学基础。据信，这些障碍是 当系统性肿瘤表达通常只在 神经元，导致有效的抗肿瘤免疫和自身免疫神经元 退化。我们已经利用了血清中存在的高滴度抗体 对PND患者的脑脊液和脑脊液进行疾病分类和靶点识别 抗原。然而，降低抗体效价的治疗方案显示 无临床反应，被动转移抗体或诱导 动物的抗体反应不会复制这种疾病。我们建议 探讨B细胞和T细胞在临床疾病中的作用 特别是，我们怀疑并将专门搜索以前的 不明原因的T细胞成分导致了这种疾病。在初步研究中，我们 已经能够找到一种特定的细胞毒性T细胞免疫的证据 几例PND患者血清和脊髓液的反应。我们会 试图改变自身免疫反应以改善临床 结果，监测临床和免疫学参数。