title: Altered T cell phenotypes associated with clinical relapse of multiple sclerosis patients receiving fingolimod therapy.
abstract: Multiple sclerosis (MS) is a T cell-mediated autoimmune disease. Fingolimod, a highly effective disease-modifying drug for MS, retains CCR7+central memory T cells in which autoaggressive T cells putatively exist, in secondary lymphoid organs, although relapse may still occur in some patients. Here, we analyzed the T cell phenotypes of fingolimod-treated, fingolimod-untreated patients, and healthy subjects. The frequency of CD56+T cells and granzyme B-, perforin-, and Fas ligand-positive T cells significantly increased during fingolimod treatment. Each T cell subpopulation further increased during relapse. Interestingly, T cells from fingolimod-treated patients exhibited interferon-γ biased production, and more myelin basic protein-reactive cells was noted in CD56+than in CD56-T cells. It is likely that the altered T cell phenotypes play a role in MS relapse in fingolimod-treated patients. Further clinical studies are necessary to investigate whether altered T cell phenotypes are a biomarker for relapse under fingolimod therapy.
authors.affiliation: Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Fujii
authors.affiliation: Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.|Department of Clinical Network and Collaborative Medicine, Kyoto University Hospital, Kyoto, Japan.|Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Department of Neurology, Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, Osaka, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Neurology and Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hashi
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.|Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Shin-Ya
authors.affiliation: Department of Neurology, Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, Osaka, Japan.
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Department of Neurology, North Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Mizuno
mesh_terms: D000328:Adult; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D013110:Sphingosine / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine