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.