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

Rameeza Allie, Lina Hu, Katherine M. Mullen, Suhayl Dhib-Jalbut, Peter A. Calabresi

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Background: Glatiramer acetate therapy is thought to be effective for multiple sclerosis (MS) by promoting TH2 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 TH2 cytokine biased, consistent with previous studies. We found a significant reduction in the expression of the TH1 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.

Original languageEnglish (US)
Pages (from-to)889-894
Number of pages6
JournalArchives of Neurology
Volume62
Issue number6
DOIs
StatePublished - Jun 1 2005

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All Science Journal Classification (ASJC) codes

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

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