Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy

J Clin Invest. 1997 Jun 1;99(11):2664-71. doi: 10.1172/JCI119455.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Adult
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / pathology*
  • B7-1 Antigen*
  • Cell Count / drug effects
  • Female
  • Flow Cytometry
  • Humans
  • Interferon beta-1a
  • Interferon beta-1b
  • Interferon-beta / therapeutic use*
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology

Substances

  • Adjuvants, Immunologic
  • B7-1 Antigen
  • Interferon beta-1b
  • Interferon-beta
  • Interferon beta-1a