Mechanism of induction of immune tolerance in experimental autoimmune encephalomyelitis by combination treatment with fingolimod plus pathogenic autoantigen. Issue 1 (22nd August 2014)

• Record Type: Journal Article
• Authors: Yoshida, Yuya; Mikami, Norihisa; Tsuji, Takumi; Takada, Yuki; Nakazawa, Yuka; Dan, Rie; Takatsuji, Miku; Fujita, Tetsuro; Tsujikawa, Kazutake; Kohno, Takeyuki
• Is Part Of: Clinical & experimental neuroimmunology. Volume 6:Issue 1(2015)
• Page Start: 49
• Page End: 56
• Publication Date: 2014-08-22
• Subjects: 616.80479
• DOI: 10.1111/cen3.12140
• Languages: English
• ISSNs: 1759-1961

Abstract

<abstract abstract-type="main" id="cen312140-abs-0001"> <title>Abstract</title> <sec id="cen312140-sec-0001" sec-type="section"> <title>Objective</title> <p>We previously reported that relapse of experimental autoimmune encephalomyelitis (EAE) occurred approximately 1 week after discontinuation of fingolimod (FTY720), but combination treatment with FTY720 plus pathogenic autoantigen significantly suppressed occurrence of relapse. Here, we investigated the mechanism of this suppression.</p> </sec> <sec id="cen312140-sec-0002" sec-type="section"> <title>Methods</title> <p>EAE mice were treated from onset with FTY720 alone or in combination with an autoantigenic peptide of myelin oligodendrocyte glycoprotein 35(MEVGWYRSPFSRVVHLYRNGK)55 (MOG<sub>35‐55</sub>). Antigen‐specific T cell activity and T cell subpopulations were analyzed by using flow cytometric analysis. Spinal cords were excised and examined immunohistochemically.</p> </sec> <sec id="cen312140-sec-0003" sec-type="section"> <title>Results</title> <p>After treatment with FTY720 alone, CD4<sup>+</sup> T cells from inguinal lymph nodes (LN) maintained activity towards pathogenic autoantigen. The percentage of CD4<sup>+</sup>CD44<sup>high</sup>CD62L<sup>low</sup> (effector memory) T cells in inguinal LN was significantly increased. At day 8 after discontinuation, infiltration of CD3<sup>+</sup> and CD4<sup>+</sup> cells in spinal cords was significantly increased, and the absolute number of CD4<sup>+</sup> T cells in inguinal LN was decreased. However, in the case of combination treatment, the absolute number of CD4<sup>+</sup> T cells in inguinal LN remained unchanged, and infiltration of CD3<sup>+</sup> and CD4<sup>+</sup> cells was significantly suppressed.</p> </sec> <sec id="cen312140-sec-0004" sec-type="section"> <title>Conclusions</title> <p>As the number of CD4<sup>+</sup> T cells in inguinal LN was unchanged in the FTY720 plus MOG<sub>35‐55</sub> group, the combination treatment might inhibit relapse by decreasing the ability of pathogenic T cells to migrate from peripheral tissues to the central nervous system. The combination treatment might become a breakthrough remission‐induction treatment for MS.</p> </sec> </abstract>