Pathogenic CD8(+) T cells in multiple sclerosis.
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.
Friese
Manuel A
MA
Institut für Neuroimmunologie und Klinische Multiple Sklerose-Forschung, Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. manuel.friese@zmnh.uni-hamburg.de
Fugger
Lars
L
D000483:Alleles; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism; D005805:Genes, MHC Class I; D006801:Humans; D008959:Models, Neurological; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D016207:Cytokines