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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们在LCMV感染的小鼠中证实，抗CD 137介导的抑制可以在CD 8 T细胞以及CD 4 T细胞中诱导。使用P14 TCR转基因T细胞和CD 137缺陷小鼠，我们已经表明，由抗CD 137引起的抑制的诱导不依赖于T细胞上的CD 137表达，并且靶细胞类型可能是树突状细胞的子集。发现这些DC上的CD 137的交联诱导Stat 3磷酸化，这是已知抑制DC和B细胞成熟和功能的事件。我们的研究集中在细胞的基础上，免疫抑制诱导后注射激动剂抗CD 137。我们还在流感病毒感染和存活模型中证实，注射抗CD 137的小鼠经历了80%的死亡率，而使用相同的感染剂量，只有20%的对照小鼠死于感染。