Relapse of Experimental Autoimmune Encephalomyelitis after Discontinuation of FTY720 (Fingolimod) Treatment, but Not after Combination of FTY720 and Pathogenic Autoantigen
Relapse of Experimental Autoimmune Encephalomyelitis after Discontinuation of FTY720 (Fingolimod) Treatment, but Not after Combination of FTY720 and Pathogenic Autoantigen
复制标题
DOI：
10.1248/bpb.34.933
复制
发表时间：
2011-06-01
影响因子：
2
通讯作者：
Kohno, Takeyuki
中科院分区：
文献类型：
--
作者：
Yoshida, Yuya;Tsuji, Takumi;Kohno, Takeyuki
FTY720 （Fingolimod）已知对实验性自身免疫性脑脊髓炎（EAE）具有显著的治疗作用。本研究采用髓鞘少突胶质细胞糖蛋白部分肽（MOG(35-55)）免疫C57BL/6J小鼠建立EAE小鼠模型，观察FTY720单独或联合MOG治疗停止后EAE的复发情况（35-55）。所有动物（n=6）在停用FTY720后一周内均出现复发，淋巴细胞浸润脊髓数量增加，脱髓鞘。然而，在FTY720和MOG联合治疗的情况下（35-55），停药后的复发被完全抑制。自身抗原肽可能抑制复发相关自身抗原特异性T细胞的克隆选择。
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 (MOG(35-55)), to examine the relapse of EAE upon discontinuation of treatment with FTY720 alone or in combination with MOG(35-55). 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 MOG(35-55), 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.