Glatiramer acetate induces a Th2-biased response and crossreactivity with myelin basic protein in patients with MS
- 1 August 2001
- journal article
- research article
- Published by SAGE Publications in Multiple Sclerosis Journal
- Vol. 7 (4) , 209-219
- https://doi.org/10.1177/135245850100700401
Abstract
Glatiramer acetate (GA) is an approved treatment for multiple sclerosis (MS). The proposed mechanism of action is the induction of GA-specific T cells characterized by protective anti-inflammatory Th2 response. We tested this hypothesis in 11 MS patients treated with GA from 1-19 months. Interferon-g and IL-5 (markers of Th1 and Th2 responses respectively) were assayed by ELISA in GA-specific T-cell lines (TCL) supernatants. Th1/Th2 bias was defined based on the ratio of IFN-γ/IL-5 secretion. Fifty-eight pre-treatment, and 75 on-treatment GA-specific TCL were generated. On-treatment mean IL-5 levels in GA-TCL increased significantly, whereas those for IFN-g were markedly reduced. Consequently, the ratio of IFN-γ/IL-5 also shifted in favor of a Th2 response. The percentage of GA-TCL classified as Th1 was decreased, whereas those classified as Th2 increased on-treatment as compared to pre-treatment. Some GA-specific TCL, (approximately 25%) generated during treatment secreted predominantly IL-5 in response to MBP and the immunodominant MBP peptide 83-99, indicating that these crossreactive antigens can act as partial agonists for GA-reactive TCL. These results strongly suggest that the mechanism of action of GA in MS involves the induction of crossreactive GA-specific T cells with a predominant Th2 cytokine profile.Keywords
This publication has 35 references indexed in Scilit:
- Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disabilityNeurology, 1998
- Copolymer 1 inhibits chronic relapsing experimental allergic encephalomyelitis induced by proteolipid protein (PLP) peptides in mice and interferes with PLP-specific T cell responsesJournal of Neuroimmunology, 1996
- Copolymer 1 reduces relapse rate and improves disability in relapsing‐remitting multiple sclerosisNeurology, 1995
- Direct binding of myelin basic protein and synthetic copolymer 1 to class II major histocompatibility complex molecules on living antigen-presenting cells--specificity and promiscuity.Proceedings of the National Academy of Sciences, 1994
- Synthetic copolymer 1 inhibits human T-cell lines specific for myelin basic protein.Proceedings of the National Academy of Sciences, 1992
- Specific inhibition of the T-cell response to myelin basic protein by the synthetic copolymer Cop 1.Proceedings of the National Academy of Sciences, 1988
- A Pilot Trial of Cop 1 in Exacerbating–Remitting Multiple SclerosisNew England Journal of Medicine, 1987
- Effect of treatment with copolymer 1 (Cop-1) on the in vivo and in vitro manifestations of experimental allergic encephalomyelitis (EAE)Journal of the Neurological Sciences, 1983
- Suppression of experimental allergic encephalomyelitis in rhesus monkeys by a synthetic basic copolymerClinical Immunology and Immunopathology, 1974
- Suppression of experimental allergic encephalomyelitis by a synthetic polypeptideEuropean Journal of Immunology, 1971