LOCAL CONTROL OF IMMUNE ACTIVITY IN THE BRAIN

大脑免疫活动的局部控制

• 批准号: 6392321
• 负责人: LOIS ALTERMAN LAMPSON
• 金额: $ 27.09万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6392321
• 关键词: T lymphocyte; brain stem; cell line; cryostat; cytokine receptors; disease /disorder model; drug adverse effect; glioma; immunoregulation; interferon gamma; laboratory rat; major histocompatibility complex; microglia; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplastic growth; neuroimmunomodulation; neuropeptide receptor; neuroregulation; stainings; stereotaxic techniques; substance P

DESCRIPTION (Applicant's Abstract): Neuropeptides can affect leukocytes in vitro and immune responses in vivo. Here the question asked is, do local neuropeptides affect immune behavior within the brain itself? The investigators study two key features of the T cell-mediated response: T-cell entry, and expression of the MHC proteins that present antigens to T cells. They examine MHC expression and T cell entry in normal rats, and at sites of brain tumor growth. The neuropeptide the investigators are studying is substance P (SP). The local site they study is the brain stem. Brain stem glioma is an important and devastating tumor, particularly in childhood. The tumor's location and growth pattern make T-cell mediated therapy of special interest. SP is abundant in the brain stem. Here they define its local immunologic effects. This work has basic and clinical interest. Hypotheses: (1) Immune regulation in the normal brain is site-specific. (2) Immune regulation is still possible, and still site-specific, in the presence of growing tumor. (3) The local neuro-regulatory environment contributes to site-specific regulation. In particular, the immune-enhancing neuropeptide, substance P (SP), can enhance IFN-g's effects. Methods: T cell entry, MHC expression, T-cell/tumor interactions are studied quantitatively, using the model developed by the investigators. Methods include stereotactic injection, antibody staining of cryostat sections, and computer-assisted image analysis. Rats are used.

描述（申请人的摘要）：神经肽可以影响白细胞 体外和体内的免疫反应。 这里问的问题是，做本地 神经肽影响大脑本身的免疫行为？ 这 研究人员研究了 T 细胞介导的反应的两个关键特征： T 细胞进入以及向 T 呈递抗原的 MHC 蛋白的表达 细胞。 他们检查了正常大鼠的 MHC 表达和 T 细胞进入，并在 脑肿瘤生长部位。 研究人员正在研究的神经肽 研究的是P物质（SP）。 他们研究的局部部位是脑干。 脑干胶质瘤是一种重要且具有破坏性的肿瘤，特别是在 童年。 肿瘤的位置和生长模式使得 T 细胞介导 特别感兴趣的疗法。 SP在脑干中含量丰富。 在这里他们 定义其局部免疫效应。 本工作具有基础和临床 兴趣。 假设：（1）正常大脑的免疫调节是 特定地点。 （2）免疫调节仍然是可能的，并且仍然 特定部位，在肿瘤生长的情况下。 (3) 当地 神经调节环境有助于位点特异性调节。 在 特别是，免疫增强神经肽 P 物质 (SP) 可以增强 IFN-g 的作用。 方法：T 细胞进入、MHC 表达、T 细胞/肿瘤 使用开发的模型定量研究相互作用 调查人员。 方法包括立体定向注射、抗体染色 低温切片和计算机辅助图像分析。 使用老鼠。