Cross-Recognition of a Myelin Peptide by CD8+ T Cells in the CNS Is Not Sufficient to Promote Neuronal Damage

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 (MOG 40–54 ) 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.