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lüll Knocking at the brain s door: intravital two-photon imaging of autoreactive T cell interactions with CNS structures Kawakami N; Flugel ASemin Immunopathol 2010[Sep]; 32 (3): 275-87Since the first applications of two-photon microscopy in immunology 10 years ago, the number of studies using this advanced technology has increased dramatically. The two-photon microscope allows long-term visualization of cell motility in the living tissue with minimal phototoxicity. Using this technique, we examined brain autoantigen-specific T cell behavior in experimental autoimmune encephalitomyelitis, the animal model of human multiple sclerosis. Even before disease symptoms appear, the autoreactive T cells arrive at their target organ. There they crawl along the intraluminal surface of central nervous system (CNS) blood vessels before they extravasate. In the perivascular environment, the T cells meet phagocytes that present autoantigens. This contact activates the T cells to penetrate deep into the CNS parenchyma, where the infiltrated T cells again can find antigen, be further activated, and produce cytokines, resulting in massive immune cell recruitment and clinical disease.|*Autoimmunity[MESH]|Animals[MESH]|Blood-Brain Barrier/immunology/pathology[MESH]|Brain/*cytology/*immunology[MESH]|Cell Movement/immunology[MESH]|Encephalomyelitis, Autoimmune, Experimental/immunology/pathology[MESH]|Fluorescent Dyes[MESH]|Humans[MESH]|Microscopy, Fluorescence, Multiphoton/instrumentation/*methods[MESH]|Multiple Sclerosis/immunology/pathology[MESH]|T-Lymphocytes/*immunology[MESH] |