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

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Item Type:Article
Title:Cross-recognition of a myelin peptide by CD8(+) T cells in the CNS is not sufficient to promote neuronal damage
Creators Name:Reuter, E. and Gollan, R. and Grohmann, N. and Paterka, M. and Salmon, H. and Birkenstock, J. and Richers, S. and Leuenberger, T. and Brandt, A.U. and Kuhlmann, T. and Zipp, F. and Siffrin, V.
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, Animals, Mice
Source:Journal of Neuroscience
Publisher:Society for Neuroscience
Page Range:4837-4850
Date:25 March 2015
Official Publication:https://doi.org/10.1523/JNEUROSCI.3380-14.2015
PubMed:View item in PubMed

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