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.