Regulation of CD4 T cell antigen sensitivity by cytokines

细胞因子调节 CD4 T 细胞抗原敏感性

• 批准号: RGPIN-2016-04713
• 负责人: Richer, Martin
• 金额: $ 2.26万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=684036
• 关键词: Regulation; CD4; cell; antigen; sensitivity

The immune system contains several cell subsets, including T cells, which must be orchestrated properly in order to defend the host against infection. T cells become activated when they encounter a peptide for which they are specific. In order to become fully activated, T cells need to receive at least three different signals. Among these are signals delivered by small proteins generated over the course of an infection, called cytokines. Cytokines are becoming more and more understood to play a critical role in the biology of T cells. We are interested in how these signals are integrated by T cells to regulate their function. In particular, we are interested in how one type of T cells, CD4 T cells, integrate signals from cytokines differently than another related cell type, CD8 T cells. Thus, the main goal of our research program is to understand the impact of cytokine signaling on the biology of CD4 T cells and to elucidate the pathways that are activated downstream of these signals. We will address whether changes in the quality, quantity and timing of signals transmitted by cytokines differentially impact the function of CD4 T cells. In particular, in this research proposal we will concentrate on how signals from cytokines can help CD4 T cells to respond to low concentrations of antigen, a characteristic called antigen sensitivity. Our work will provide novel knowledge that will help us understand how all the signals that T cells receive work together to regulate their function. Understanding the impact of cytokine signaling on CD4 T cells will provide a platform for the development of new biotechnologies to manipulate CD4 T cell function. Thus, this research will yield important intellectual and economic dividends for Canada.

免疫系统包含多个细胞亚群，包括 T 细胞，它们必须正确协调才能保护宿主免受感染。当 T 细胞遇到它们特异的肽时，它们就会被激活。为了完全激活，T 细胞需要接收至少三种不同的信号。其中包括感染过程中产生的小蛋白质（称为细胞因子）传递的信号。人们越来越认识到细胞因子在 T 细胞生物学中发挥着关键作用。我们感兴趣的是 T 细胞如何整合这些信号来调节其功能。我们特别感兴趣的是一种类型的 T 细胞（CD4 T 细胞）如何以不同于另一种相关细胞类型（CD8 T 细胞）的方式整合来自细胞因子的信号。因此，我们研究项目的主要目标是了解细胞因子信号传导对 CD4 T 细胞生物学的影响，并阐明这些信号下游激活的途径。我们将探讨细胞因子传递信号的质量、数量和时间的变化是否对 CD4 T 细胞的功能产生不同的影响。特别是，在这项研究计划中，我们将重点关注细胞因子的信号如何帮助 CD4 T 细胞对低浓度抗原做出反应，这一特性称为抗原敏感性。我们的工作将提供新颖的知识，帮助我们了解 T 细胞接收到的所有信号如何协同工作来调节其功能。了解细胞因子信号转导对 CD4 T 细胞的影响将为开发操纵 CD4 T 细胞功能的新生物技术提供平台。因此，这项研究将为加拿大带来重要的智力和经济红利。