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Multiple sclerosis: glatiramer acetate induces anti-inflammatory T cells in the cerebrospinal fluid

Faculty of Medicine, Institute of Immunology, Rikshospitalet-Radiumhospitalet, Oslo, Norway, a.l.k.hestvik{at}medisin.uio.no

G Skorstad

Department of Neurology, Ullevål University Hospital, Oslo, Norway

DA Price

Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK

F Vartdal

Faculty of Medicine, Institute of Immunology, Rikshospitalet-Radiumhospitalet, Oslo, Norway

T Holmoy

Faculty of Medicine, Institute of Immunology, Rikshospitalet-Radiumhospitalet, Oslo, Norway; Department of Neurology, Ullevål University Hospital, Oslo, Norway

Glatiramer acetate (GA) is believed to induce GA-reactive T cells that secrete anti-inflammatory cytokines at the site of inflammation in multiple sclerosis (MS). However, GA-reactive T cells have not been established from the intrathecal compartment of MS patients, and intrathecal T cells may differ from T cells in blood. Here, we compared the phenotype of GA-reactive T cells from the cerebrospinal fluid (CSF) and blood of five MS patients treated with GA for 3-36 months, and in three of these patients also before treatment. From the CSF of these patients, all 22 T cell lines generated before and all 38 T cell lines generated during treatment were GA-reactive. GA treatment induced a more pronounced anti-inflammatory profile of GA-reactive T cell lines from CSF than from blood. While GA-reactive T cell clones from CSF were restricted by either human leukocyte antigen (HLA) -DR or HLA-DP, only HLA-DR restricted GA-reactive T cell clones were detected in blood. No cross reactivity with myelin proteins was detected in GA-reactive T cell lines or clones from CSF. These results suggest that a selected subset of GA-reactive T cells are present in the intrathecal compartment, and support an anti-inflammatory mechanism of action for GA.

Key Words: multiple sclerosis; immunology; glatiramer acetate; disease modifying therapies

Multiple Sclerosis, Vol. 14, No. 6, 749-758 (2008)
DOI: 10.1177/1352458508089411


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