Non-Invasive Imaging of T Cell Trafficking

描述（由申请方提供）：小鼠接触性超敏反应（CHSR）是原型迟发型超敏反应（DTHR），广泛用于研究T淋巴细胞介导的炎症。皮肤DTHR由产生干扰素γ的CD4+（Th1）和CD8+（Tc1）细胞介导，所述细胞保护免受细胞内病原体的侵害或在针对肿瘤相关抗原（Ag）时产生治疗效果。Th1和Tc1细胞在针对皮肤上的器官特异性自身抗原或半抗原时可能变得有害。在DTHR过程中，对Th1和Tc1细胞的运输模式以及皮肤和其他组织中T细胞增殖的位点知之甚少。在这里，我们解决动态的T细胞迁移在体内使用过继转移的Ag特异性Th1细胞。对于这些实验，在耳处的Ag攻击之前，幼稚小鼠接受放射性标记的感兴趣的T细胞以分析它们的迁移。这些研究将显示Th1细胞进入组织和它们在耳组织中迁移的确切顺序和动力学。耳和引流耳淋巴结可以很容易地定位现代成像技术，如高分辨率正电子发射断层扫描（PET）。PET是一种独特的技术，用于在体内非侵入性追踪放射性标记的细胞，以分析T细胞从特异性免疫应答的开始直到终止的命运。由于标记细胞的数量和标记剂的量是有限的，灵敏度和准确的定量是一个关键问题。将使用放射自显影或经典生物分布方法等侵入性比较测量对体内数据进行定量评价。此外，将为无创PET成像开发针对部分容积效应的特定校正方法和校准测量。这项工作包括生物学和生物医学工程两个不同学科的两个主要问题：获得Th1细胞介导的炎症的生物信息和建立定量的非侵入性PET成像的细胞运输和细胞增殖，在体内。

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.