Glatiramer acetate induces a Th2-biased response and crossreactivity with myelin basic protein in patients with MS

M. Chen, B. Gran, K. Costello, K. Johnson, R. Martin, S. Dhib-Jalbut

Research output: Contribution to journalArticlepeer-review

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-γ 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-γ 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.

Original languageEnglish (US)
Pages (from-to)209-219
Number of pages11
JournalMultiple Sclerosis
Volume7
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Copaxone®
  • Copolymer-I
  • Glatiramer acetate
  • Immune deviation
  • Multiple sclerosis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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