Bioluminescence imaging to monitor T cell localization

描述（由申请人提供）：我们建议在此开发的生物发光成像（BLI）方法为接触敏感性（CS）和迟发型超敏反应（DTH）研究提供了实质性益处，并向更广泛的科学家群体开放了免疫反应和炎症研究领域。此外，我们提出的研究可能会为专注于关节炎小动物模型的研究带来重大改进。从本质上讲，我们建议开发的BLI方法引入了更客观和侵入性更小的方法来评估局部炎症。此外，预计这些研究的结果将使这些测量更加容易和客观。因此，可以预期，它将促进基础研究，并使商业开发的小动物炎症模型的药物发现和临床前疗效的目的。 我们建议进行的生物学研究将为炎症过程提供新的线索，并有望进一步了解T细胞如何参与这些过程。此外，我们建议为这些研究开发并广泛使用的转基因小鼠将在我们的实验室和其他地方开辟炎症研究的新途径。 本项目的工作范围包括在CDS启动子控制下开发表达荧光素酶的转基因小鼠。当T细胞迁移到炎症部位如DTH和CS中的耳朵或关节炎情况下的关节时，该构建体在转基因小鼠的T细胞中独特地表达，通过Illuminecense成像使T细胞可视化到关节，因为这些T细胞中的荧光素酶产生可被成像设备检测到的可见光。这些转基因小鼠的开发使得本项目中定义的生物学研究和其他实验室的生物学研究成为可能。

DESCRIPTION (provided by applicant): The Bioluminescence Imaging (BLI) methods that we propose to develop here offer substantial benefits for Contact Sensitivity (CS) and Delayed Type Hypersensitivity (DTH) studies and open this area of immune response and inflammation research to a much broader group of scientists. In addition, the studies we propose potentially introduce significant improvements for investigations focused on small animal models of arthritis. In essence, the BLI methods we propose to develop introduce more objective and less invasive methods for evaluating local inflammation. In addition, results from these studies can be expected to introduce greater ease and objectivity into these measurements. Thus, it can be expected to facilitate basic studies and to enable commercial exploitation of small animal inflammation models for drug discovery and preclinical efficacy purposes. The biological studies that we propose to conduct will shed new light on inflammatory processes and can be expected to further understanding of how T cells participate in these processes. In addition, the transgenic mice that we propose to develop for these studies and to make broadly available will open new avenues of inflammation research in our laboratory and elsewhere. The work-scope in this project involves development of transgenic mice expressive luciferase under the control of the CDS promoter. This construct is expressed uniquely in the T-cells of the transgenic mice when the T-cells migrate to sites of inflammation such as the ears in DTH and CS or to joints in the case of arthritis by illuminecense imaging visualizes the T-cells to the joint because luciferase in these T-cells generates visible light that can be detected by the imaging equipment. Development of these transgenic mice enables the biological studies defined in this project and biological studies other laboratories.