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Rameeza Allie, MS; Lina Hu, PhD; Katherine M. Mullen, BA; Suhayl Dhib-Jalbut, MD; Peter A. Calabresi, MD

Arch Neurol. 2005;62:889-894.

Background  Glatiramer acetate therapy is thought to be effective for multiple sclerosis (MS) by promoting T_H2 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_H2 cytokine biased, consistent with previous studies. We found a significant reduction in the expression of the T_H1 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.

Author Affiliations: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Md (Drs Hu and Calabresi and Mss Allie and Mullin); and Department of Neurology, University of Medicine and Dentistry of New Jersey, New Brunswick (Dr Dhib-Jalbut).

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