Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy.
Costimulatory molecules help determine T cell responses. CD80 (B7-1) and CD86 (B7-2), costimulatory proteins on antigen-presenting cells, bind to CD28 on T cells. When costimulation is coupled with a signal through the T cell receptor (TCR), T cell proliferation and cytokine secretion are induced. However, TCR signaling without CD80/CD86CD28 costimulation causes anergy. During multiple sclerosis (MS) exacerbations, circulating immune cells are activated, Th1 cytokine levels in the blood are elevated, and blood-derived immune cells destroy brain oligodendroglia. In the experimental autoimmune encephalomyelitis model of MS, CD80 on antigen-presenting cells induces Th1 cell responses; CD86 enhances generation of Th2 cells. Variation in CD80 and CD86 expression is likely to influence immune regulation in MS. We demonstrate that the number of circulating CD80(+) lymphocytes is increased significantly during MS exacerbations, but is normal in stable MS. These CD80(+) lymphocytes are predominantly B cells, based on two-color flow cytometry. The number of CD71(+) and HLA-DR+ lymphocytes and monocytes is also increased in active MS. Therapy with IFN beta-1b markedly reduces the number of circulating CD80(+) B cells and increases CD86(+) monocyte number. HLA-DR+, CD71(+), and CD25(+) mononuclear cell numbers are also reduced by therapy. The number of CD80(+) cells may be a useful surrogate marker during IFN-beta therapy, and reduction of CD80-mediated costimulation may be one therapeutic mechanism by which IFN-beta acts in MS.
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Department of Neurology, and the Brain Research Institute, University of Chicago, Chicago, Illinois 60637, USA.
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D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D018122:B7-1 Antigen; D002452:Cell Count / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a