title: Cross-recognition of a myelin peptide by CD8+ T cells in the CNS is not sufficient to promote neuronal damage.
abstract: Multiple sclerosis (MS) is an inflammatory disease of the CNS thought to be driven by CNS-specific T lymphocytes. Although CD8(+) T cells are frequently found in multiple sclerosis lesions, their distinct role remains controversial because direct signs of cytotoxicity have not been confirmed in vivo. In the present work, we determined that murine ovalbumin-transgenic (OT-1) CD8(+) T cells recognize the myelin peptide myelin oligodendrocyte glycoprotein 40-54 (MOG40-54) both in vitro and in vivo. The aim of this study was to investigate whether such cross-recognizing CD8(+) T cells are capable of inducing CNS damage in vivo. Using intravital two-photon microscopy in the mouse model of multiple sclerosis, we detected antigen recognition motility of the OT-1 CD8(+) T cells within the CNS leading to a selective enrichment in inflammatory lesions. However, this cross-reactivity of OT-1 CD8(+) T cells with MOG peptide in the CNS did not result in clinically or subclinically significant damage, which is different from myelin-specific CD4(+) Th17-mediated autoimmune pathology. Therefore, intravital imaging demonstrates that local myelin recognition by autoreactive CD8(+) T cells in inflammatory CNS lesions alone is not sufficient to induce disability or increase axonal injury.
authors: Department of Neurology, Research Center Translational Neurosciences, Rhine Main Neuroscience Network (rmn), and.
authors: Eva
authors: E
authors: Reuter
authors: Department of Neurology, Research Center Translational Neurosciences, Rhine Main Neuroscience Network (rmn), and.
authors: René
authors: R
authors: Gollan
authors: Molecular Neurology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, 13125 Berlin, Germany, Charité University Medicine Berlin, ECRC, 13125 Berlin, Germany, and.
authors: Nadia
authors: http://orcid.org/0000-0003-1582-2739
authors: N
authors: Grohmann
authors: Department of Neurology, Research Center Translational Neurosciences, Rhine Main Neuroscience Network (rmn), and Molecular Neurology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, 13125 Berlin, Germany.
authors: Magdalena
authors: M
authors: Paterka
authors: Charité University Medicine Berlin, ECRC, 13125 Berlin, Germany, and.
authors: Hélène
authors: http://orcid.org/0000-0002-2253-3807
authors: H
authors: Salmon
authors: Department of Neurology, Research Center Translational Neurosciences, Rhine Main Neuroscience Network (rmn), and.
authors: Jérôme
authors: J
authors: Birkenstock
authors: Institute of Microanatomy and Neurobiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
authors: Sebastian
authors: S
authors: Richers
authors: Department of Neurology, Research Center Translational Neurosciences, Rhine Main Neuroscience Network (rmn), and Molecular Neurology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, 13125 Berlin, Germany.
authors: Tina
authors: T
authors: Leuenberger
authors: Molecular Neurology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, 13125 Berlin, Germany, Charité University Medicine Berlin, ECRC, 13125 Berlin, Germany, and.
authors: Alexander U
authors: AU
authors: Brandt
authors: Institute of Neuropathology, University Hospital Münster, 48149 Münster, Germany.
authors: Tanja
authors: T
authors: Kuhlmann
authors: Department of Neurology, Research Center Translational Neurosciences, Rhine Main Neuroscience Network (rmn), and Molecular Neurology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, 13125 Berlin, Germany.
authors: Frauke
authors: http://orcid.org/0000-0002-1231-1928
authors: F
authors: Zipp
authors: Department of Neurology, Research Center Translational Neurosciences, Rhine Main Neuroscience Network (rmn), and Molecular Neurology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, 13125 Berlin, Germany, Charité University Medicine Berlin, ECRC, 13125 Berlin, Germany, and siffrinv@gmx.de.
authors: Volker
authors: V
authors: Siffrin
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016923:Cell Death; D049109:Cell Proliferation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology*; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D009410:Nerve Degeneration / Q000276:immunology*
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein
keywords: CD8+ T cells; EAE/MS; intravital microscopy; molecular mimicry