Induction of apoptosis of CD4+ T cells by immunomodulatory therapy of multiple sclerosis with glatiramer acetate

Eur Neurol. 2003;50(4):200-6. doi: 10.1159/000073860.

Abstract

Glatiramer acetate (GA), a mixture of synthetic polypeptides, has beneficial effects on the clinical course and the MRI-defined disease activity of patients with multiple sclerosis (MS). In MS, evidence has been provided that the apoptosis of disease-relevant T cells is dysregulated. In this study, we investigated the effect of GA on T cell apoptosis, T cell activation, and cytokine profile of lymphocytes derived from 19 relapsing-remitting MS patients during the first year of GA therapy. Analysis of blood samples obtained every 6 weeks showed an increase in apoptotic T helper cells after 30 weeks of therapy. This effect remained until the end of the study and was accompanied by an increase in activated T cells and interleukin-4-producing lymphocytes. Thus, in addition to the established effect of GA on the cytokine network, GA-mediated immunomodulation might involve the apoptotic elimination of T helper cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Apoptosis*
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / drug effects
  • Female
  • Flow Cytometry / methods
  • Glatiramer Acetate
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Lectins, C-Type
  • Male
  • Multiple Sclerosis / drug therapy*
  • Peptides / therapeutic use*
  • Time Factors

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD69 antigen
  • Immunosuppressive Agents
  • Lectins, C-Type
  • Peptides
  • Interleukin-4
  • Glatiramer Acetate
  • Interferon-gamma