title: Relapse of experimental autoimmune encephalomyelitis after discontinuation of FTY720 (Fingolimod) treatment, but not after combination of FTY720 and pathogenic autoantigen.
abstract: FTY720 (Fingolimod) is known to have a significant therapeutic effect on experimental autoimmune encephalomyelitis (EAE). Here, we used an EAE mouse model, which had been established by immunizing C57BL/6J mice with a partial peptide of myelin oligodendrocyte glycoprotein (MOG₃₅₋₅₅), to examine the relapse of EAE upon discontinuation of treatment with FTY720 alone or in combination with MOG₃₅₋₅₅. Relapse was confirmed to occur in all animals (n=6) within one week after discontinuation of FTY720, with increase in the number of lymphocytes infiltrating the spinal cord and demyelination. However, in the case of combination therapy with FTY720 and MOG₃₅₋₅₅, relapse following discontinuation of treatment was completely suppressed. The autoantigenic peptide might serve to suppress the clonal selection of relapse-associated autoantigen-specific T cells.
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Takumi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Fujita
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Kohno
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D003711:Demyelinating Diseases / Q000209:etiology; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D005260:Female; D000068876:Fingolimod Hydrochloride; D006023:Glycoproteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011409:Propylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D012074:Remission Induction; D055502:Secondary Prevention; D013047:Specific Pathogen-Free Organisms; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D001324:Autoantigens; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011409:Propylene Glycols; C445081:myelin oligodendrocyte glycoprotein (35-55); D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine