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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 + CD25 high CD127 low ) 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 ( p corr  =0.0834).    Conclusions  The CD4 + TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.

Peripheral Blood T Cell Dynamics Predict Relapse in Multiple Sclerosis Patients on Fingolimod