title: Modulation of immune function occurs within hours of therapy initiation for multiple sclerosis.
abstract: Daily administration of FDA-approved glatiramer acetate (GA) has beneficial effects on clinical course of relapsing remitting multiple sclerosis (RRMS). Although mechanisms of GA-action have been widely investigated and partially understood, immediate immune dynamics following GA-therapy are unknown. In the present study, we characterized the immediate effects of GA on phenotype, quantity and function of immune cells in MS patients. Prominent changes in immune cells were detected within 4-12h post-first GA-injection. T-cell modulation included significantly decreased CD4/CD8 ratio, perturbed homeostasis of predominantly CD8+ T-cells, significant enhancement in CD8+ T-cell mediated suppression and inhibitory potential of induced CD4-suppressors. Changes in APC were restricted to monocytes and included reduced stimulatory capacity in MLR and significantly increased IL-10 and TNF-α production. Our study provides the first evidence that GA treatment induces rapid immunologic changes within hours of first dose. Interestingly, these responses are not only restricted to innate immune cells but also include complex modulation of T-cell functionality.
authors.affiliation: Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390-9072, USA.
authors.forename: Chris L
authors.initials: CL
authors.lastname: Ayers
authors.forename: Jason P
authors.initials: JP
authors.lastname: Mendoza
authors.forename: Sushmita
authors.initials: S
authors.lastname: Sinha
authors.forename: Khrishen
authors.initials: K
authors.lastname: Cunnusamy
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Greenberg
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Frohman
authors.forename: Nitin J
authors.initials: NJ
authors.lastname: Karandikar
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D010455:Peptides / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000068717:Glatiramer Acetate