Bystander modulation of chemokine receptor expression on peripheral blood T lymphocytes mediated by glatiramer therapy

Arch Neurol. 2005 Jun;62(6):889-94. doi: 10.1001/archneur.62.6.889.


Background: Glatiramer acetate therapy is thought to be effective for multiple sclerosis (MS) by promoting T(H)2 cytokine deviation, possibly in the brain, but the exact mechanism and site of action are incompletely understood. Determining the site of action and effect of glatiramer on cell trafficking is of major importance in designing rational combination therapy clinical trials.

Objective: To determine whether glatiramer therapy will also act in the peripheral blood through bystander modulation of chemokine receptor (CKR) expression and cytokine production on T lymphocytes.

Design: Before-and-after trial.

Setting: A university MS specialty center.

Patients: Ten patients with relapsing-remitting MS.

Interventions: Treatment with glatiramer for 12 months and serial phlebotomy.

Main outcome measures: Cytokine production, CKR expression, and cell migration.

Results: The glatiramer-reactive T cells were T(H)2 cytokine biased, consistent with previous studies. We found a significant reduction in the expression of the T(H)1 inflammation associated with the CKRs CXCR3, CXCR6, and CCR5 on glatiramer- and myelin-reactive T cells generated from patients with MS receiving glatiramer therapy vs baseline. Conversely, expression of the lymph node-homing CKR, CCR7, was markedly enhanced on the glatiramer-reactive T cells derived from patients with MS undergoing glatiramer therapy. There was a reduction in the percentage of CD4+ glatiramer-reactive T cells and an increase in the number of CD8+ glatiramer-reactive T cells.

Conclusions: Glatiramer may suppress autoreactive CD4+ effector memory T cells and enhance CD8+ regulatory responses, and bystander modulation of CKRs may occur in the periphery.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bystander Effect / drug effects*
  • Bystander Effect / immunology*
  • Glatiramer Acetate
  • Humans
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Multiple Sclerosis, Relapsing-Remitting / metabolism
  • Peptides / pharmacology*
  • Peptides / therapeutic use*
  • Receptors, Chemokine / biosynthesis*
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / immunology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • Peptides
  • Receptors, Chemokine
  • Glatiramer Acetate