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.
Highlights
TCM in CSF14 are associated with clinical relapses during fingolimod therapy
We intensively studied surface molecules on peripheral blood (PB) T cells from fingolimod-treated Multiple sclerosis (MS) (F-MS) patients, interferon (IFN)-β-treated patient, patients not treated with disease modifying dugs (DMD) and healthy subjects (HS) (Table 1)
The first striking finding in this study is that the frequency of CD56+ T cells increased in fingolimod-treated patients, which was not observed in patients without MS-DMD and IFN-βtherapy
Summary
TCM in CSF14 are associated with clinical relapses during fingolimod therapy. It is possible that relapse while receiving fingolimod has other underlying immunopathological mechanisms than the insufficient reduction of TCM. There is another observation to indicate distinct pathomechanisms of the therapy-associated relapse. It was reported that relapsed lesions during fingolimod therapy tended to be unusually severe or tumefactive[15,16,17]. We investigated the phenotypic and functional characteristics of peripheral blood T cells in patients undergoing fingolimod therapy both in remission and at relapse cpmpared with fingolimod-untreated MS patients and healthy subjects. We propose that altered T cell phenotypes are associated with relapse under fingolimod therapy
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