Abstract
BackgroundFingolimod 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 FindingsBlood 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+CD25highCD127low) 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 (pcorr=0.0834).ConclusionsThe CD4+TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.
Highlights
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and is assumed to be an autoimmune disease targeting myelin [1]
The CD4+TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse
Fingolimod efficiently reduces multiple sclerosis (MS) relapse by inhibiting lymphocyte egress from lymph nodes through downmodulation of sphingosine 1-phosphate (S1P) receptors [2,3], which is consistent with findings in an animal model of MS that fingolimod successfully reduced the infiltration of myelin antigen-specific CD4+T (CD28-) cells (Ts) cells into inflammatory sites in experimental autoimmune encephalomyelitis [4]
Summary
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and is assumed to be an autoimmune disease targeting myelin [1]. Fingolimod efficiently reduces MS relapse by inhibiting lymphocyte egress from lymph nodes through downmodulation of sphingosine 1-phosphate (S1P) receptors [2,3], which is consistent with findings in an animal model of MS that fingolimod successfully reduced the infiltration of myelin antigen-specific CD4+T cells into inflammatory sites in experimental autoimmune encephalomyelitis [4]. We aimed to clarify the alterations in peripheral blood T cell subsets during short-term and long-term treatment periods, which are associated with therapeutic efficacy or treatment failure including suboptimal responses during fingolimod therapy. 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
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