Inflammatory potential and migratory capacities across human brain endothelial cells of distinct glatiramer acetate-reactive T cells generated in treated multiple sclerosis patients

Clin Immunol. 2004 Apr;111(1):38-46. doi: 10.1016/j.clim.2004.01.004.

Abstract

We asked whether GA-reactive T cells with distinct cytokine profiles (Th2 versus Th1/Th0), induced during GA therapy of multiple sclerosis (MS) patients, have different migratory capacities across human brain endothelial cells (HBECs), and distinct effects on inflammatory responses at the level of the blood-brain barrier (BBB). We confirmed that GA therapy induces a range of GA-reactive T cells defined by distinct profiles of cytokine expression. Supernatants from Th0/Th1 GA-reactive cells significantly upregulated pro-inflammatory chemokine and adhesion molecule expression in HBECs. Post-treatment Th2-polarized GA-reactive cells were significantly less pro-inflammatory but did not suppress the effects induced by Th1 cells. All lines migrated across a HBEC/fibronectin-based model of the BBB with similar efficiencies. We conclude that the spectrum of GA-reactive T cells induced in treated MS patients may differentially impact inflammatory responses at the BBB level. Future studies will determine whether this could contribute to variable clinical response to GA therapy.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Blood-Brain Barrier / physiology
  • Brain / metabolism*
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / drug effects
  • Cell Line
  • Cell Movement
  • Cytokines / biosynthesis
  • Cytokines / drug effects
  • Cytokines / immunology
  • Endothelial Cells / metabolism*
  • Glatiramer Acetate
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Inflammation
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology*
  • Peptides / therapeutic use*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Cell Adhesion Molecules
  • Cytokines
  • Immunosuppressive Agents
  • Peptides
  • Glatiramer Acetate