Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod.

Fingolimod efficiently reduces multiple sclerosis (MS) relapse by inhibiting lymphocyte egress from lymph nodes through down-modulation of sphingosine 1-phosphate (S1P) receptors. We aimed to clarify the alterations in peripheral blood T cell subsets associated with MS relapse on fingolimod.Blood sa...

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Main Authors: Zi-Ye Song, Ryo Yamasaki, Yuji Kawano, Shinya Sato, Katsuhisa Masaki, Satoshi Yoshimura, Dai Matsuse, Hiroyuki Murai, Takuya Matsushita, Jun-ichi Kira
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4412716?pdf=render
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author Zi-Ye Song
Ryo Yamasaki
Yuji Kawano
Shinya Sato
Katsuhisa Masaki
Satoshi Yoshimura
Dai Matsuse
Hiroyuki Murai
Takuya Matsushita
Jun-ichi Kira
author_facet Zi-Ye Song
Ryo Yamasaki
Yuji Kawano
Shinya Sato
Katsuhisa Masaki
Satoshi Yoshimura
Dai Matsuse
Hiroyuki Murai
Takuya Matsushita
Jun-ichi Kira
author_sort Zi-Ye Song
collection DOAJ
description Fingolimod efficiently reduces multiple sclerosis (MS) relapse by inhibiting lymphocyte egress from lymph nodes through down-modulation of sphingosine 1-phosphate (S1P) receptors. We aimed to clarify the alterations in peripheral blood T cell subsets associated with MS relapse on fingolimod.Blood samples successively collected from 23 relapsing-remitting MS patients before and during fingolimod therapy (0.5 mg/day) for 12 months and 18 healthy controls (HCs) were analysed for T cell subsets by flow cytometry. In MS patients, the percentages of central memory T (CCR7+CD45RO+) cells (TCM) and naïve T (CCR7+CD45RO-) cells decreased significantly, while those of effector memory T (CCR7-CD45RA-) and suppressor precursor T (CD28-) cells increased in both CD4+T and CD8+T cells from 2 weeks to 12 months during fingolimod therapy. The percentages of regulatory T (CD4+CD25highCD127low) cells in CD4+T cells and CCR7-CD45RA+T cells in CD8+T cells also increased significantly. Eight relapsed patients demonstrated greater percentages of CD4+TCM than 15 non-relapsed patients at 3 and 6 months (p=0.0051 and p=0.0088, respectively). The IL17-, IL9-, and IL4-producing CD4+T cell percentages were significantly higher at pre-treatment in MS patients compared with HCs (p<0.01 for all), while the IL17-producing CD4+T cell percentages tended to show a transient increase at 2 weeks of fingolimod therapy (pcorr=0.0834).The CD4+TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.
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spelling doaj.art-ba39fc9fcabd435982a67dd37289ce152022-12-22T03:04:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01104e012492310.1371/journal.pone.0124923Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod.Zi-Ye SongRyo YamasakiYuji KawanoShinya SatoKatsuhisa MasakiSatoshi YoshimuraDai MatsuseHiroyuki MuraiTakuya MatsushitaJun-ichi KiraFingolimod efficiently reduces multiple sclerosis (MS) relapse by inhibiting lymphocyte egress from lymph nodes through down-modulation of sphingosine 1-phosphate (S1P) receptors. We aimed to clarify the alterations in peripheral blood T cell subsets associated with MS relapse on fingolimod.Blood samples successively collected from 23 relapsing-remitting MS patients before and during fingolimod therapy (0.5 mg/day) for 12 months and 18 healthy controls (HCs) were analysed for T cell subsets by flow cytometry. In MS patients, the percentages of central memory T (CCR7+CD45RO+) cells (TCM) and naïve T (CCR7+CD45RO-) cells decreased significantly, while those of effector memory T (CCR7-CD45RA-) and suppressor precursor T (CD28-) cells increased in both CD4+T and CD8+T cells from 2 weeks to 12 months during fingolimod therapy. The percentages of regulatory T (CD4+CD25highCD127low) cells in CD4+T cells and CCR7-CD45RA+T cells in CD8+T cells also increased significantly. Eight relapsed patients demonstrated greater percentages of CD4+TCM than 15 non-relapsed patients at 3 and 6 months (p=0.0051 and p=0.0088, respectively). The IL17-, IL9-, and IL4-producing CD4+T cell percentages were significantly higher at pre-treatment in MS patients compared with HCs (p<0.01 for all), while the IL17-producing CD4+T cell percentages tended to show a transient increase at 2 weeks of fingolimod therapy (pcorr=0.0834).The CD4+TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.http://europepmc.org/articles/PMC4412716?pdf=render
spellingShingle Zi-Ye Song
Ryo Yamasaki
Yuji Kawano
Shinya Sato
Katsuhisa Masaki
Satoshi Yoshimura
Dai Matsuse
Hiroyuki Murai
Takuya Matsushita
Jun-ichi Kira
Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod.
PLoS ONE
title Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod.
title_full Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod.
title_fullStr Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod.
title_full_unstemmed Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod.
title_short Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod.
title_sort peripheral blood t cell dynamics predict relapse in multiple sclerosis patients on fingolimod
url http://europepmc.org/articles/PMC4412716?pdf=render
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