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

Zi Ye Song, Ryo Yamasaki, Yuji Kawano, Shinya Sato, Katsuhisa Masaki, Satoshi Yoshimura, Dai Matsuse, Hiroyuki Murai, Takuya Matsushita, Jun-Ichi Kira

研究成果: ジャーナルへの寄稿記事

37 引用 (Scopus)

抄録

Background: 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. Methods/Principal Findings: 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). Conclusions: The CD4+TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.

元の言語英語
記事番号e0124923
ジャーナルPloS one
10
発行部数4
DOI
出版物ステータス出版済み - 4 28 2015

Fingerprint

T-cells
relapse
sclerosis
blood cells
Multiple Sclerosis
Blood Cells
Blood
T-lymphocytes
T-Lymphocytes
Recurrence
T-Lymphocyte Subsets
therapeutics
Interleukin-9
Lysosphingolipid Receptors
T-Lymphoid Precursor Cells
Therapeutics
Relapsing-Remitting Multiple Sclerosis
Data storage equipment
Interleukin-4
Lymphocytes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

これを引用

Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod. / Song, Zi Ye; Yamasaki, Ryo; Kawano, Yuji; Sato, Shinya; Masaki, Katsuhisa; Yoshimura, Satoshi; Matsuse, Dai; Murai, Hiroyuki; Matsushita, Takuya; Kira, Jun-Ichi.

:: PloS one, 巻 10, 番号 4, e0124923, 28.04.2015.

研究成果: ジャーナルへの寄稿記事

@article{8b2599d515f4467b8227b191d58fe204,
title = "Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod",
abstract = "Background: 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. Methods/Principal Findings: 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 na{\"i}ve 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). Conclusions: The CD4+TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.",
author = "Song, {Zi Ye} and Ryo Yamasaki and Yuji Kawano and Shinya Sato and Katsuhisa Masaki and Satoshi Yoshimura and Dai Matsuse and Hiroyuki Murai and Takuya Matsushita and Jun-Ichi Kira",
year = "2015",
month = "4",
day = "28",
doi = "10.1371/journal.pone.0124923",
language = "English",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod

AU - Song, Zi Ye

AU - Yamasaki, Ryo

AU - Kawano, Yuji

AU - Sato, Shinya

AU - Masaki, Katsuhisa

AU - Yoshimura, Satoshi

AU - Matsuse, Dai

AU - Murai, Hiroyuki

AU - Matsushita, Takuya

AU - Kira, Jun-Ichi

PY - 2015/4/28

Y1 - 2015/4/28

N2 - Background: 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. Methods/Principal Findings: 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). Conclusions: The CD4+TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.

AB - Background: 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. Methods/Principal Findings: 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). Conclusions: The CD4+TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.

UR - http://www.scopus.com/inward/record.url?scp=84928692825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928692825&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0124923

DO - 10.1371/journal.pone.0124923

M3 - Article

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e0124923

ER -