Cytokine production in T lymphocyte-microglia interaction is attenuated by glatiramer acetate: a mechanism for therapeutic efficacy in multiple sclerosis.
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 dose 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.
Chabot
S
S
Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Alberta, Canada.
Yong
F P
FP
Le
D M
DM
Metz
L M
LM
Myles
T
T
Yong
V W
VW
D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology; D017628:Microglia / Q000166:cytology*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D010455:Peptides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism
D016207:Cytokines; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate