LOCAL CONTROL OF IMMUNE ACTIVITY IN THE BRAIN

大脑免疫活动的局部控制

• 批准号: 6185851
• 负责人: LOIS ALTERMAN LAMPSON
• 金额: $ 26.3万
• 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 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6185851
• 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， 体外和体内免疫应答。 这里要问的问题是， 神经肽影响大脑自身的免疫行为？ 的 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，以及将抗原呈递给T细胞的MHC蛋白的表达。 细胞 他们检测了正常大鼠的MHC表达和T细胞进入， 脑肿瘤生长的部位。 研究人员正在研究的神经肽 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的和毁灭性的肿瘤，特别是在 童年. 肿瘤的位置和生长方式使T细胞介导的 特别感兴趣的治疗。 SP在脑干中含量丰富。 这里他们 确定其局部免疫效应。 这项工作有基础和临床 兴趣 假设：（1）正常大脑中的免疫调节是 特定地点。 (2)免疫调节仍然是可能的， 在肿瘤生长的情况下，具有位点特异性。 (3)当地 神经调节环境有助于位点特异性调节。 在 特别是免疫增强性神经肽P物质（SP）， IFN-G的作用 方法：T细胞进入，MHC表达，T细胞/肿瘤 相互作用进行了定量研究，使用模型开发的 investigators. 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。 老鼠被利用了。