Regulation of CD4 T cell antigen sensitivity by cytokines

免疫系统包含几个细胞亚群，包括T细胞，它们必须经过适当的协调才能保护宿主免受感染。当T细胞遇到特定的肽时，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。这些信号是由感染过程中产生的小蛋白质传递的，称为细胞因子。细胞因子在T细胞的生物学中起着至关重要的作用。我们感兴趣的是T细胞如何整合这些信号来调节它们的功能。我们特别感兴趣的是一种类型的T细胞，CD4 T细胞，如何整合来自细胞因子的信号，不同于另一种相关的细胞类型，CD8 T细胞。因此，我们研究计划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的信号的质量、数量和时间的变化是否会对CD4 T细胞的功能产生不同的影响。特别是，在本研究计划中，我们将集中研究细胞因子的信号如何帮助CD4 T细胞对低浓度的抗原作出反应，这种特征称为抗原敏感性。我们的工作将提供新的知识，帮助我们理解T细胞接收的所有信号是如何协同工作来调节它们的功能的。了解细胞因子信号传导对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一个平台。因此，这项研究将为加拿大带来重要的知识和经济红利。

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.