title: Glatiramer acetate induces a Th2-biased response and crossreactivity with myelin basic protein in patients with MS.
abstract: Glatiromer 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-gamma 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-gamma/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-gamma were markedly reduced. Consequently, the ratio of IFN-gamma 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.
authors.affiliation: University of Maryland School of Medicine, Baltimore 21201, USA.
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: B
authors.initials: B
authors.lastname: Gran
authors.forename: K
authors.initials: K
authors.lastname: Costello
authors.forename: K
authors.initials: K
authors.lastname: Johnson
authors.forename: R
authors.initials: R
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Dhib-Jalbut
mesh_terms: D002460:Cell Line; D003429:Cross Reactions; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015848:Interleukin-5 / Q000096:biosynthesis; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D010455:Peptides / Q000494:pharmacology*; D012044:Regression Analysis; D013601:T-Lymphocytes / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D015848:Interleukin-5; D004676:Myelin Basic Protein; D010455:Peptides; D000068717:Glatiramer Acetate