The process of lymphocyte migration is fundamental to the function of the immune system. We have pioneered in the development of methodologies to visualize the immune response within the eye at the level of a single cell using intravital microscopy and models of anterior uveitis that utilize T cells which are transgenic for a specific peptide. To build on our observations to date, we propose to 1) test the hypothesis that specific chemokines, chemokine receptors, and adhesion molecules are involved in the rolling, arrest, and extravasation of CD4 T lymphocytes that characterize anterior uveitis; 2) test several hypotheses regarding the migration of T cells within the iris stroma at a site of inflammation including characterizing the interaction between T cells and antigen-presenting cells in this site; and 3) test the hypothesis that CD8 cells will be fundamentally similar to CD4 cells in their migratory behavior in these models. The studies which we propose will integrate principles of immunology and ophthalmology with technical advances in image analysis and microscropy including the use of image stabilization and two-photon microscopy. These studies should result in a fundamental improvement in the understanding of how T cells behave within a site of inflammation. ? ? ?
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