Bioluminescence imaging to monitor T cell localization

描述（由申请人提供）：我们在这里提出开发的生物发光成像（BLI）方法为接触敏感性（CS）和延迟型超敏反应（DTH）研究提供了实质性的好处，并为更广泛的科学家群体打开了免疫反应和炎症研究的这一领域。此外，我们提出的研究可能会为关节炎小动物模型的研究带来重大改进。从本质上讲，我们提出的BLI方法为评估局部炎症提供了更客观、侵入性更小的方法。此外，这些研究的结果有望使这些测量更加容易和客观。因此，它可以促进基础研究，并使小动物炎症模型的商业开发用于药物发现和临床前疗效目的。我们提出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为我们实验室和其他地方的炎症研究开辟新的途径。本课题的工作范围是在CDS启动子的控制下，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的耳朵或关节炎的关节时，这种结构在转基因小鼠的t细胞中唯一表达，通过发光成像将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见光，可以被成像设备检测到。这些转基因小鼠的发展使本项目界定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.