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Cytokine production in T lymphocyte-microglia interaction is attenuated by glatiramer acetate: a mechanism for therapeutic efficacy in multiple sclerosis

Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

F P Yong

Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

D M Le

Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

L M Metz

Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

T Myles

Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

V W Yong

Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada, Department of Oncology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada, vyong{at}ucalgary.ca

The efficacy of glatiramer acetate in multiple sclerosis (MS) is thought to involve the production of Th2 regulatory lymphocytes that secrete anti-inflammatory cytokines; however, other mechanisms cannot be excluded. Given that activated T lymphocytes infiltrate into the CNS and become in close proximity to microglia, we evaluated whether glatiramer acetate affects the potential interaction between T cells and microglia. We report that the co-culture of activated T lymphocytes with microglia led to the induction of several cytokines, and that these were reduced by glatiramer acetate treatment. Morphological transformation of bipolar/ramified microglia into an activated ameboid form was attenuated by glatiramer acetate. These results reveal a novel mechanism for glatiramer acetate: the impairment of activated T cells to effectively interact with microglia to produce cytokines. The net result of a non-inflammatory milieu within the CNS, in spite of T cell infiltration, may help account for the amelioration of disease activity in MS patients on glatiramer acetate therapy.

Key Words: cytokine • lymphocyte • microglia • neuroinflammation • therapeutics

Multiple Sclerosis, Vol. 8, No. 4, 299-306 (2002)
DOI: 10.1191/1352458502ms810oa


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