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An autoimmunity odyssey: how autoreactive T cells infiltrate into the CNS

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons38918

Kawakami,  Naoto
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons38757

Bartholomäus,  Ingo
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons61113

Pesic,  Marija
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons39002

Mues,  Marsilius
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

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Zitation

Kawakami, N., Bartholomäus, I., Pesic, M., & Mues, M. (2012). An autoimmunity odyssey: how autoreactive T cells infiltrate into the CNS. IMMUNOLOGICAL REVIEWS, 248(Sp. Iss.), 140-155. doi:10.1111/j.1600-065X.2012.01133.x.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-000F-C3AF-C
Zusammenfassung
Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of multiple sclerosis (MS), a human autoimmune disease. To explore how EAE and ultimately MS is induced, autoantigen-specific T cells were established, were labeled with fluorescent protein by retroviral gene transfer, and were tracked in vivo after adoptive transfer. Intravital imaging with two-photon microscopy was used to record the entire entry process of autoreactive T cells into the CNS: a small number of T cells first appear in the CNS leptomeninges before onset of EAE, and crawl on the intraluminal surface of blood vessels, which is integrin a4 and aL dependent. After extravasation, the T cells continue into the perivascular space, meeting local antigen-presenting cells (APCs), which present endogenous antigens. This interaction activates the T cells and guides them to penetrate the CNS parenchyma. As the local APCs in the CNS are not saturated with endogenous antigens, exogenous antigens stimulate the autoreactive T cells more strongly and, as a result, exacerbate the clinical outcome. Currently, we are attempting to visualize T-cell activation in vivo in both rat T-cell-mediated EAE and mouse spontaneous EAE models.