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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 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抗抑制作用。使用p14 TCR转基因T细胞和CD137缺陷小鼠，我们表明，抗CD137引起的抑制诱导与T细胞上的CD137表达无关，并且靶向细胞类型可以是树突状细胞的子集。发现这些DC上CD137的交联可诱导STAT3磷酸化，该事件已知可抑制DC和B细胞的成熟和功能。我们的研究集中于注射激动性抗CD137后免疫抑制的基础。我们还在流感病毒感染和生存模型中证实，抗CD137注射小鼠的死亡率具有80％的死亡率，而使用相同的感染剂量，只有20％的对照小鼠屈服于感染。