Non-Invasive Imaging of T Cell Trafficking

描述(申请人提供)：小鼠的接触性超敏反应(CHSR)是典型的迟发性超敏反应(DTHR)，广泛用于研究T淋巴细胞介导的炎症。皮肤DTHR是由干扰素γ产生的CD4+(Th1)和CD8+(Tc1)细胞介导的，当针对肿瘤相关抗原(Ag)时，这些细胞可以保护细胞内的病原体或发挥治疗作用。当针对器官特异性自身抗原或皮肤上的半抗原时，Th1和Tc1细胞可能会变得有害。在DTHR中，Th1和Tc1细胞的转运方式以及T细胞在皮肤和其他组织中的增殖部位尚不清楚。在这里，我们使用过继转移的抗原特异性Th1细胞来研究T细胞在体内的迁移动力学。在这些实验中，幼小鼠在耳部接受抗原攻击之前接受感兴趣的放射性标记T细胞，以分析它们的迁移。这些研究将显示Th1细胞进入组织的确切顺序和动力学，以及它们在耳朵组织中的迁移。通过现代成像技术，如高分辨率正电子发射断层扫描(PET)，可以很容易地定位耳朵和引流的耳朵淋巴结。PET是一种独特的无创示踪体内放射性标记细胞的技术，用于分析T细胞从启动到终止特定免疫反应的命运。由于标记细胞的数量和标记剂的用量有限，灵敏度和准确的定量是一个关键问题。体内数据的定量评估将使用侵入性比较测量，如放射自显影或经典的生物分布方法。此外，还将为非侵入性PET成像开发特定的校正方法和部分体积效应的校准测量。这项工作包括生物学和生物医学工程中两个不同学科的主要问题：获取Th1细胞介导的炎症的生物学信息和建立体内细胞迁移和细胞增殖的定量无创PET成像。

DESCRIPTION (provided by applicant): Contact hypersensitivity reactions (CHSR) in mice are prototypic delayed-type hypersensitivity reactions (DTHR) that are widely used to investigate T lymphocyte-mediated inflammation. Cutaneous DTHR are mediated by Interferon gamma producing CD4+ (Th1) and CD8+ (Tc1) cells that protect against intracellular pathogens or develop therapeutic effects when directed against tumor associated antigens (Ag). Th1 and Tc1 cells may become harmful when directed against organ-specific autoantigens or hapten at the skin. Little is known about the mode of Th1 and Tc1 cell trafficking and the sites of T cell proliferation in the skin and other tissues during DTHR. Here we address the dynamics of T cell migration in vivo using adoptively transferred Ag specific Th1 cells. For these experiments naive mice receive radiolabeld T cells of interest prior to Ag challenge at the ear to analyze theire migration. These studies will show the exact sequence and dynamics of Th1 cell trafficking into tissues and their migration insite the ear tissue. The ear and draining ear lymph nodes can easily be localized by modern imaging technologies, such as high resolution positron emission tomography (PET). PET is an unique technique for non-invasive tracking of radiolabeled cells in vivo to analyze the fate of T cells from the initiation till to the termination of specific immune responses. Since the number of labeled cells and the amount of labeling agent are limited, sensitivity and accurate quantification is a critical issue. Invasive comparison measurements such as autoradiography or classical biodistribution methods will be used for quantitative valuation of the in vivo data. Additionally, specific correction methods and calibration measurements for partial volume effects will be developed for the non-invasive PET imaging. This work comprises two major issues of two different disciplines in biology and biomedical engineering: Gaining biological information on inflammation mediated by Th1 cells and establishment of quantitative non-invasive PET imaging of cell trafficking and cell proliferation, in vivo.