Context-dependent calcium signaling in encephalitogenic T cells – an in vivo two-photon imaging study
| العنوان: | Context-dependent calcium signaling in encephalitogenic T cells – an in vivo two-photon imaging study |
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| المؤلفون: | Stephanie Everts, Nikolaos I. Kyratsous, Ingo Bartholomäus, Guokun Zhang, Marija Pesic, Joanna M. Watt, Naoto Kawakami, Miriam Wörner, Ping Fang, Reinhard Hohlfeld, H. Wekerle, Marsilius Mues, Joachim W. Ellwart, Isabel J. Bauer, Barry V. L. Potter |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America Proc. Natl. Acad. Sci. U.S.A. 114, E6381-E6389 (2017) |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Stromal cell, Encephalomyelitis, Autoimmune, Experimental, T-Lymphocytes, Antigen-Presenting Cells, Spleen, Autoimmunity, Biology, Lymphocyte Activation, Autoantigens, Calcium in biology, Cell Line, 03 medical and health sciences, T-cell Activation, Central Nervous System, Intracellular Calcium, Two-photon Imaging, medicine, Cytotoxic T cell, Animals, Calcium Signaling, Antigen-presenting cell, Calcium signaling, Multidisciplinary, NFATC Transcription Factors, Experimental autoimmune encephalomyelitis, Transendothelial and Transepithelial Migration, Brain, NFAT, medicine.disease, Cell biology, Rats, 030104 developmental biology, medicine.anatomical_structure, Microscopy, Fluorescence, Multiphoton, PNAS Plus, Blood-Brain Barrier, Rats, Inbred Lew, Immunology, Female |
| الوصف: | In experimental autoimmune encephalitis (EAE), autoimmune T cells are activated in the periphery before they home to the CNS. On their way, the T cells pass through a series of different cellular milieus where they receive signals that instruct them to invade their target tissues. These signals involve interaction with the surrounding stroma cells, in the presence or absence of autoantigens. To portray the serial signaling events, we studied a T-cell-mediated model of EAE combining in vivo two-photon microscopy with two different activation reporters, the FRET-based calcium biosensor Twitch1 and fluorescent NFAT. In vitro activated T cells first settle in secondary (2 degrees) lymphatic tissues (e.g., the spleen) where, in the absence of autoantigen, they establish transient contacts with stroma cells as indicated by sporadic short-lived calcium spikes. The T cells then exit the spleen for the CNS where they first roll and crawl along the luminal surface of leptomeningeal vessels without showing calcium activity. Having crossed the blood-brain barrier, the T cells scan the leptomeningeal space for autoantigen-presenting cells (APCs). Sustained contacts result in long-lasting calcium activity and NFAT translocation, a measure of full T-cell activation. This process is sensitive to anti-MHC class II antibodies. Importantly, the capacity to activate T cells is not a general property of all leptomeningeal phagocytes, but varies between individual APCs. Our results identify distinct checkpoints of T-cell activation, controlling the capacity of myelin-specific T cells to invade and attack the CNS. These processes may be valuable therapeutic targets. |
| وصف الملف: | application/pdf |
| تدمد: | 1091-6490 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3b476f2bc673a22acb3cea6e6db102bTest http://ora.ox.ac.uk/objects/uuidTest: |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f3b476f2bc673a22acb3cea6e6db102b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 |
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