Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod

• Published in: PloS one 2015-04, Vol.10 (4), p.e0124923-e0124923
• Main Authors: Song, Zi-Ye, Yamasaki, Ryo, Kawano, Yuji, Sato, Shinya, Masaki, Katsuhisa, Yoshimura, Satoshi, Matsuse, Dai, Murai, Hiroyuki, Matsushita, Takuya, Kira, Jun-ichi
• Format: Article
• Language: English
• Subjects: Adult; Autoimmune diseases; Blood; Case-Control Studies; CC chemokine receptors; CCR7 protein; CD25 antigen; CD28 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - metabolism; CD45RA antigen; CD8 antigen; Chemokines; Cytokines; Cytokines - metabolism; Cytometry; Disease; Egress; Female; Fingolimod Hydrochloride - administration & dosage; Fingolimod Hydrochloride - therapeutic use; Flow cytometry; Humans; Immunoglobulins; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - therapeutic use; Interleukin 1; Interleukin 17; Interleukin 4; Interleukin 9; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Male; Medical research; Middle Aged; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; Neurology; Patients; Peripheral blood; Phosphates; Receptors; Recurrence; Short term; Somatotropin; Sphingosine; Sphingosine 1-phosphate; T cell receptors; T cells; Therapy; Treatment Outcome; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0124923

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. 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+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