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Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion
Open accessAbstract
We tracked pathogenic myelin basic protein-specific CD4+ effector T cells in early central nervous system (CNS) lesions of experimental autoimmune encephalomyelitis (EAE) by combining two-photon imaging and fluorescence video microscopy. We made two key observations: (a) the majority of the cells (65%) moved fast (maximal speed 25 μm/min) and apparently nondirected through the compact tissue; and (b) a second group of effector T cells (35%) appeared tethered to a fixed point. Polarization of T cell receptor and adhesion molecules (lymphocyte function-associated antigen 1) towards this fixed point suggests the formation of immune synapses. Nonpathogenic, ovalbumin-specific T cells were not tethered in the CNS and did not form synapse-like contacts, but moved through the tissue. After intrathecal injection of antigen, 40% of ovalbumin-specific T cells became tethered. Conversely, injection of anti–major histocompatibility complex class II antibodies profoundly reduced the number of stationary pathogenic T cells within the CNS (to 15%). We propose that rapid penetration of the CNS parenchyma by numerous autoimmune effector T cells along with multiple autoantigen-presentation events are responsible for the fulminate development of clinical EAE.
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“Activated T cells can enter the perivascular space independent of antigen specificity (82), but are unable to traverse the astrocytic basement membrane and glia limitans.”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [82]
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Metadata
- Authors
- Kawakami, N., Nägerl, U. V., Odoardi, F., Bonhoeffer, T., Wekerle, H., & Flügel, A.
- Affiliations
- Max Planck Institute of Neurobiology (DE)
- 2Department of Cellular and Systems Neurobiology, Max-Planck-Institute of Neurobiology, 82152 Martinsried, Germany
- 1Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, 82152 Martinsried, Germany
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-06-06
- Volume
- 201
- Issue
- 11
- Pages
- 1805-1814
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2213265
- OpenAlex
- W2153979851
- Cited by
- 248
- References
- 25
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 7 · 2020: 5 · 2019: 7 · 2018: 7 · 2017: 4 · 2016: 17 · 2015: 3 · 2014: 19 · 2013: 11 · 2012: 12
- FWCI
- 15.92
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB455)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- experimental autoimmune encephalomyelitis, myelin basic protein, CD4+ T cells, autoantigen recognition, immunological synapse, CD11a/CD18, ovalbumin-specific T cells, MHC class II, autoantigen presentation, two-photon imaging
- MeSH terms
- Animals, Histocompatibility Antigens Class II, Autoantigens, Cell Communication, Cell Movement, Central Nervous System, Myelin Basic Protein, Encephalomyelitis, Autoimmune, Experimental, Guinea Pigs, Rats, Inbred Lew, Receptors, Antigen, T-Cell, CD4-Positive T-Lymphocytes, Lymphocyte Function-Associated Antigen-1, Antigen Presentation, Microscopy, Video, Microscopy, Fluorescence, Multiphoton, Rats
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