Knocking at the brain's door: intravital two-photon imaging of autoreactive T cell interactions with CNS structures.
Since 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.
Kawakami
Naoto
N
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany. kawakami@neuro.mpg.de
Flügel
Alexander
A
D000818:Animals; D015551:Autoimmunity; D001812:Blood-Brain Barrier / Q000276:immunology / Q000473:pathology; D001921:Brain / Q000166:cytology* / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D005456:Fluorescent Dyes; D006801:Humans; D036641:Microscopy, Fluorescence, Multiphoton / Q000295:instrumentation / Q000379:methods*; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D005456:Fluorescent Dyes