title: High dose antigen treatment with a peptide epitope of myelin basic protein modulates T cells in multiple sclerosis patients.
abstract: One of the auto-antigens aberrantly targeted in Multiple sclerosis is myelin basic protein (MBP). In this study, chronic progressive multiple sclerosis (CPMS) patients receiving the experimental drug MBP8298, on a compassionate care trial, were examined before and after high dose peptide treatment for their circulating regulatory T-cell numbers and their responses to the common mitogens, phytohemagglutinin and poke-weed mitogen. Peripheral blood mononuclear cells (PBMCs) isolated from these patients before treatment displayed anergy upon stimulation with phytohemagglutinin; measured through reduced proliferation, IFN-γ and IL-17A secretion in an in vitro cell culture system. 6 Weeks and 6months after treatment their PBMCs displayed a reversal of anergy with phytohemagglutinin stimulation. There was also a marked increase in their CD4(+)CD25(+hi)FoxP3(+) T-cells regulatory T-cells. These results suggest that high dose MBP8298 treatment has a profound effect on the circulating T-cells of CPMS patients, capable of reversing peripheral anergy and establishing T regulation.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Loo
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Krantz
authors.forename: Babita
authors.initials: B
authors.lastname: Agrawal
mesh_terms: D018791:CD4 Lymphocyte Count; D017635:Clonal Anergy / Q000187:drug effects; D057176:Compassionate Use Trials; D004306:Dose-Response Relationship, Immunologic; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood; D016896:Treatment Outcome
chemical_list: C508717:IL17A protein, human; C508017:IL2RA protein, human; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; C526227:MBP-8298; D007371:Interferon-gamma