Cells (Nov 2021)

Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis Patients

  • Diana Ferraro,
  • Sara De Biasi,
  • Anna Maria Simone,
  • Riccardo Orlandi,
  • Milena Nasi,
  • Francesca Vitetta,
  • Marcello Pinti,
  • Marco Fogliani,
  • Stefano Meletti,
  • Andrea Cossarizza,
  • Patrizia Sola

DOI
https://doi.org/10.3390/cells10123324
Journal volume & issue
Vol. 10, no. 12
p. 3324

Abstract

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The altered numbers and functions of cells belonging to immunoregulatory cell networks such as T regulatory (Tregs) and invariant Natural Killer T (iNKT) cells have been reported in Multiple Sclerosis (MS), an immune-mediated disease. We aimed to assess the frequencies of Tregs and iNKT cells in MS patients throughout a one-year treatment with fingolimod (FTY) and to correlate immunological data with efficacy and safety data. The percentage of Tregs (defined as Live Dead-CD3 + CD4 + FoxP3 + CD25++/CD127− cells) increased steadily throughout the year, while there was no significant difference in the absolute number or percentage of iNKT cells (defined as CD3 + CD14−CD19− Vα24-Jα18 TCR+ cells). However, out of all the iNKT cells, the CD8+ iNKT and CD4−CD8− double-negative (DN) cell percentages steadily increased, while the CD4+ iNKT cell percentages decreased significantly. The mean percentage of CD8+ T cells at all time-points was lower in patients with infections throughout the study. The numbers and percentages of DN iNKT cells were more elevated, considering all time-points, in patients who presented a clinical relapse. FTY may, therefore, exert its beneficial effect in MS patients through various mechanisms, including the increase in Tregs and in iNKT subsets with immunomodulatory potential such as CD8+ iNKT cells. The occurrence of infections was associated with lower mean CD8+ cell counts during treatment with FTY.

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