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: 7958184
• 负责人: ROBERT S MITTLER
• 金额: $ 5.67万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958184
• 关键词: Apoptosis; Bone Marrow; CD4 Positive T Lymphocytes; CD8B1 gene; Cell Lineage; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Event; Funding; Grant; HIV Infections; Immune response; Institution; Left; Ligands; Mediating; Mus; Myelopoiesis; Primates; Proteins; Reporting; Research; Research Personnel; Resources; Signal Transduction; Source; T-Lymphocyte; TNFRSF6 gene; Transgenic Organisms; Tumor Necrosis Factor Ligand Superfamily Member 6; United States National Institutes of Health; Up-Regulation; Virus; receptor

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. In the current reporting period we confirmed that anti-CD137-mediated suppression could be induced in CD8 T cells, as well as CD4 T. By adoptively transferring CD137-sufficient SMARTA transgenic CD4 T cells and CD137-sufficient P14 TCR transgenic CD8 T cells into CD137-deficient mice and we have found that the induction of suppression caused by anti-CD137 was in part dependent on CD137 expression on T cells, rather than completely independent, as we had previously reported. The contribution made by CD137 signaling to T cells was found to be the upregulation of the apoptosis-inducing death receptor CD95 (Fas). In addition, we found that CD137-mediated signaling in pDCs and mDCs was critical to the induction of tolerance of virus-specific CD8 T cells and that DCs contributed to the induction of CD8 T cell tolerance by inducing the release of soluble Fas ligand. We showed that although DCs induced the release of soluble Fas ligand, they were not the source of this protein. Our studies are presently focused on the identification of the cell lineage that is responsible for the release of Fas ligand. In other studies we have found that CD137 and its cognate ligand function as gate keepers and limit the extent of early myelopoiesis in the bone marrow, an event that limits the numbers of DCs that leave the bone marrow and enter the periphery. This approach will advance our understanding of immune response of conditions such as HIV 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。 在当前的报告期内，我们证实，CD8 T细胞以及CD4T可以诱导抗CD137介导的抑制。通过过继转移CD137足够的CD137 SMARTA转基因CD4 T细胞和CD137失去的P14 TCR TCR TRCR CD8 T细胞中的CD137 TCR CD8 T细胞中，该细胞由CD137缺乏的小鼠造成的垂直于诱导的垂直偶导致，我们已经建立了诱因，从而构建了tt的诱因。如我们先前报道的那样，CD137在T细胞上的表达，而不是完全独立。发现CD137信号对T细胞的贡献是诱导凋亡受体CD95（FAS）的上调。 此外，我们发现PDC和MDC中CD137介导的信号传导对于诱导病毒特异性CD8 T细胞的耐受性至关重要，并且DCS通过诱导可溶性FAS配体的释放来促进CD8 T细胞耐受性。我们表明，尽管DCS诱导了可溶性FAS配体的释放，但它们并不是该蛋白质的来源。 目前，我们的研究集中在鉴定导致FAS配体释放的细胞谱系上。在其他研究中，我们发现CD137及其同源配体功能充当栅极守护者，并限制骨髓中骨髓骨气的早期程度，这一事件限制了离开骨髓并进入周围的DC的数量。 这种方法将提高我们对诸如HIV感染等疾病的免疫反应的理解。