Regulation of T cell homeostasis by IFN-gamma

IFN-γ 对 T 细胞稳态的调节

• 批准号: 7747962
• 负责人: John T Harty
• 金额: $ 35.81万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7747962
• 关键词: Address; Adoptive Transfer; Ampicillin; Antigens; Apoptosis; Biological Models; Biology; CD8B1 gene; Cells; Characteristics; Communicable Diseases; Contracts; Data; Exhibits; Funding; Gene Targeting; Generations; Genes; Goals; Grant; Homeostasis; Infection; Interferon Gamma Receptor Complex; Interferon Type II; Interferon-alpha; Interleukin-18; Listeria monocytogenes; Mediating; Memory; Messenger RNA; Microarray Analysis; Modeling; Molecular; Mus; Pathway interactions; Phase; Play; Production; Protein p53; Proteins; Receptor Signaling; Role; Signal Transduction; Signaling Molecule; Source; T cell regulation; T cell response; T-Lymphocyte; TP53 gene; Time; Tumor Suppressor Genes; Vaccination; Virus Diseases; base; cellular targeting; cost; cytokine; interleukin-18 receptor; novel; pathogen; receptor; transcription factor

During the initial funding period for this proposal, we made substantial progress in developing novel model systems to identify the specific aspects of T cell homeostasis that are influenced by IFN-gamma. Strikingly, these studies reveal that IFN-gamma produced after infection is able to regulate the initial expansion of antigen-specific CD8 T cells, the contraction phase and the rate at which T cells acquire memory characteristics. These data underlie and support our overall hypothesis for the current proposal, that that IFN-gamma is a major regulator of T cell homeostasis after infection. In this proposal, we will employ the model systems we developed in the preceding funding period to address the cellular and molecular basis for IFN-gamma regulation of T cell contraction. In addition, we will extend our studies to address the cross- talk between IFN-alpha-beta receptor and IFN-gamma receptor signaling in regulating the expansion of CDS T cells after infection. Our long-term goal is to understand how IFN-gamma and other signaling molecules regulate specific aspects of T cell homeostasis, such that this information can be used to enhance the T cell response to vaccination. Improvements in vaccination will allow the most cost effectiveand widespread defense against infectious disease. We will address our long-term goal through the following specific aims: Specific Aim 1. Determine the timing, source, quantity and cellular targets of IFN-gamma required to regulate CDST cell contraction. Specific Aim 2. Determine if IFN-gamma regulates T cell contraction through p53 and/or IL-18 signaling. Specific Aim 3. Determine the requirements for IFN-alpha-beta and IFN-gamma signaling in regulating CDS T cell expansion.

在这项建议的最初资助期间，我们在开发新的 模型系统，以确定受IFN-γ影响的T细胞稳态的具体方面。 引人注目的是，这些研究表明，感染后产生的IFN-γ能够调节最初的 抗原特异性CD 8 T细胞的扩增、收缩期和T细胞获得免疫应答的速率 记忆特性这些数据支持我们对当前提案的总体假设，即 IFN-γ是感染后T细胞稳态的主要调节因子。在本提案中，我们将采用 我们在前一个资助期开发的模型系统，以解决细胞和分子基础 用于IFN-γ调节T细胞收缩。此外，我们将扩大我们的研究，以解决交叉- IFN-α-β受体和IFN-γ受体信号在调节CDS扩增中的作用 感染后的T细胞我们的长期目标是了解IFN-γ和其他信号分子如何 调节T细胞稳态的特定方面，使得该信息可用于增强T细胞免疫应答。 接种疫苗的反应。疫苗接种的改进将使最具成本效益和最广泛的 防御传染病。我们将通过以下具体目标实现我们的长期目标： 具体目标1.确定IFN-γ的时间、来源、数量和细胞靶点， 调节CDST细胞收缩。 具体目标2。确定IFN-γ是否通过p53和/或IL-18信号调节T细胞收缩。 具体目标3。确定在调节CDS中IFN-α-β和IFN-γ信号传导的要求 T细胞扩增。