title: The dynamics of mucosal-associated invariant T cells in multiple sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination, gliosis and axonal loss in the Central Nervous System. Although the etiology of the disease has remained enigmatic, recent studies have suggested a role of the innate-like T cells, called Mucosal Associated Invariant T cells (MAITs) in the pathophysiology. In the present study, we have analyzed the relative frequency of MAITs and the expression of the cell surface antigens in MAITs to seek a possible link to the disease.
  
  
  RESULTS
  There was little difference in the frequency of total MAITs between healthy donors (HDs) and untreated MS patients, whereas the latter harbored more CD8(lo/neg) (DN) MAITs concomitant with a decrease in CD8(high) MAITs and in CD4 MAITs compared with those in HDs. While the expression of CCR5, CCR6, CD95, CD127, and CD150 has increased in untreated subjects compared with that in HDs, CD45RO has declined in untreated subjects in both DN MAITs and CD8(hi) MAITs. FTY720 therapy has increased the relative frequency of total MAITs in a time-dependent fashion up to 2 years. Intriguingly, FTY720 therapy for 3 years reversed the above phenotype, engendering more CD8(high) MAITs accompanied with decreased DN MAITs. FTY720 therapy affected the cytokine production from CD4 T cells and also enhanced the relative frequency of cells producing both TNF-α and IFN-γ from MAITs, CD8 T cells, and CD4 T cells compared with that in untreated subjects.
  
  
  CONCLUSIONS
  FTY 720 therapy enhanced the relative frequency of MAITs in MS patients in a time-dependent manner. Although the expression of CD8 in MAITs has been affected early by FTY720, longer treatment has reversed the phenotypic change. These data demonstrated that FTY720 induced dynamic change in the relative frequency and in the phenotype of MAITs in MS.
authors.affiliation: Department of Hygiene & Cellular Preventive Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Sugimoto
authors.affiliation: Department of Neurology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirotani
authors.affiliation: Asubio Pharma Co Ltd, Kobe, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yoshikiyo
authors.affiliation: Asubio Pharma Co Ltd, Kobe, Japan.
authors.forename: Uichi
authors.initials: U
authors.lastname: Koshimizu
authors.affiliation: Pharmaceutical and Medical Device Agency (PMDA), Tokyo, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Wakao
authors.affiliation: Department of Cellular Pharmacology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Horinouchi
authors.affiliation: Department of Cellular Pharmacology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Mazaki
authors.affiliation: Department of Cellular Pharmacology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Higashi
authors.affiliation: Sapporo Neurology Hospital, Sapporo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukazawa
authors.affiliation: Department of Hygiene & Cellular Preventive Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Department of Neurology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Hidenao
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Hygiene & Cellular Preventive Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakao
keywords: Disease-modifying therapy; FTY720; Mucosal associated invariant T cells; Multiple sclerosis; Phenotyping