2. Academic Validation
  3. Cross-recognition of a myelin peptide by CD8+ T cells in the CNS is not sufficient to promote neuronal damage

Cross-recognition of a myelin peptide by CD8+ T cells in the CNS is not sufficient to promote neuronal damage

  • J Neurosci. 2015 Mar 25;35(12):4837-50. doi: 10.1523/JNEUROSCI.3380-14.2015.
Eva Reuter 1,  René Gollan 1,  Nadia Grohmann 2,  Magdalena Paterka 3,  Hélène Salmon 4,  Jérôme Birkenstock 1,  Sebastian Richers 5,  Tina Leuenberger 3,  Alexander U Brandt 2,  Tanja Kuhlmann 6,  Frauke Zipp 3,  Volker Siffrin 7
Affiliations

Affiliations

  • 1 Department of Neurology, Research Center Translational Neurosciences, Rhine Main Neuroscience Network (rmn), and.
  • 2 Molecular Neurology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, 13125 Berlin, Germany, Charité University Medicine Berlin, ECRC, 13125 Berlin, Germany, and.
  • 3 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.
  • 4 Charité University Medicine Berlin, ECRC, 13125 Berlin, Germany, and.
  • 5 Institute of Microanatomy and Neurobiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
  • 6 Institute of Neuropathology, University Hospital Münster, 48149 Münster, Germany.
  • 7 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 [email protected].
PMID: 25810515 DOI: 10.1523/JNEUROSCI.3380-14.2015
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.

Keywords

CD8+ T cells; EAE/MS; intravital microscopy; molecular mimicry.

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