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Pathogenic CD8+ T cells in multiple sclerosis

Authors

  • Manuel A. Friese MD,

    Corresponding author
    1. Institut für Neuroimmunologie und Klinische Multiple Sklerose-Forschung, Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
    2. Department of Clinical Neurology, John Radcliffe Hospital, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
    • Institut für Neuroimmunologie und Klinische Multiple Sklerose-Forschung, Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany
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  • Lars Fugger MD, PhD

    Corresponding author
    1. Department of Clinical Neurology, John Radcliffe Hospital, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
    2. Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
    3. Clinical Institute, Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark
    • Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headley Way, Oxford OX3 9DS, United Kingdom
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  • Potential conflict of interest: Nothing to report.

Abstract

Traditionally, autoimmune pathogeneses have been attributed to CD4+ T lymphocytes, as in multiple sclerosis (MS), rheumatoid arthritis, type 1 diabetes mellitus, and/or to B lymphocytes, as in myasthenia gravis and systemic lupus erythematosus. That is because their primary genetic associations are mostly with certain human leukocyte antigen class II alleles, whose gene products present antigens to CD4+ T cells. Because few autoimmune diseases show stronger associations with major histocompatibility complex class I alleles (ankylosing spondylitis, Behçet's disease, and psoriasis), CD8+ T cells, which interact with major histocompatibility complex class I molecules, have been largely ignored in autoimmunity research. However, a variety of findings has recently revived interest in this population, particularly in MS. First, it shows associations with major histocompatibility complex class I alleles. Second, its lesions show a predominance of CD8+ T cells. Third, these represent effectors that can directly damage central nervous system target cells. Furthermore, several clinical trials of monoclonal antibodies specifically against CD4+ T cells, or the polarizing cytokines on which they depend, have failed to show any therapeutic benefit in MS, unlike broader-spectrum antibodies that deplete all T cells. Here, we review the evidence that CD8+ T cells play a role in MS pathogenesis. Ann Neurol 2009;66:132–141

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