CD137 SIGNALS IN DC DURING AG-PRIMING INDUCES TOLERANCE

AG 启动期间 DC 中的 CD137 信号会导致容差

• 批准号: 7562629
• 负责人: ROBERT S MITTLER
• 金额: $ 3.95万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562629
• 关键词: B-Lymphocytes; CD4 Positive T Lymphocytes; CD8B1 gene; Cell Maturation; Computer Retrieval of Information on Scientific Projects Database; Dendritic Cells; Dose; Event; Funding; Grant; Immune; Infection; Injection of therapeutic agent; Institution; Lymphocytic choriomeningitis virus; Modeling; Mus; Phosphorylation; Rate; Research; Research Personnel; Resources; Signal Transduction; Source; T-Lymphocyte; Transgenic Organisms; United States National Institutes of Health; Virus Diseases; base; cell type; crosslink; experience; influenzavirus; mortality

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We confirmed in LCMV infected mice that anti-CD137-meidated suppression can be induced in CD8 T cells, as well as CD4 T cells. Using P14 TCR transgenic T cells and CD137-deficient mice we have shown that the induction of suppression caused by anti-CD137 is independent of CD137 expression on T cells, and that the targeted cell type could be a subset of dendritic cells. Crosslinking of CD137 on these DC was found to induce Stat3 phosphorylation, an event known to suppress DC and B cell maturation and function. Our studies focus on the cellular basis that underlies the induction of immune suppression following injection of agonistic anti-CD137. We also confirmed in an influenza virus infection and survival model that anti-CD137 injected mice experienced an 80% mortality rate whereas using the same infectious dose, only 20% of control mice succumbed to infection.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们在 LCMV 感染的小鼠中证实，可以在 CD8 T 细胞以及 CD4 T 细胞中诱导抗 CD137 介导的抑制。使用 P14 TCR 转基因 T 细胞和 CD137 缺陷小鼠，我们发现抗 CD137 引起的抑制的诱导与 T 细胞上的 CD137 表达无关，并且目标细胞类型可能是树突状细胞的子集。发现这些 DC 上 CD137 的交联会诱导 Stat3 磷酸化，这是一种已知会抑制 DC 和 B 细胞成熟和功能的事件。我们的研究重点是注射激动性抗 CD137 后诱导免疫抑制的细胞基础。我们还在流感病毒感染和生存模型中证实，注射抗 CD137 的小鼠死亡率为 80%，而使用相同的感染剂量，只有 20% 的对照小鼠死于感染。