Pathogenic CD8(+) T cells in multiple sclerosis.

Journal article

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.

Authors: Friese, M; Fugger, L

• Publication status: Published
• Journal: Annals of neurology
• Volume: 66
• Issue: 2
• Pages: 132-141
• Publication date: 2009-08-01
• DOI: 10.1002/ana.21744
• EISSN: 1531-8249
• ISSN: 0364-5134
• Language: English
• Keywords: Alleles; CD8-Positive T-Lymphocytes; Animals; Genes, MHC Class I; Antibodies, Monoclonal; Spinal Cord; Models, Neurological; Cytokines; CD4-Positive T-Lymphocytes; Brain; Humans; Clinical Trials as Topic; Multiple Sclerosis