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.
| Kneilling, Manfred; Mailhammer, Reinhard; Hultner, Lothar et al. (2009) Direct crosstalk between mast cell-TNF and TNFR1-expressing endothelia mediates local tissue inflammation. Blood 114:1696-706 |
