Newly produced T and B lymphocytes and T-cell receptor repertoire diversity are reduced in peripheral blood of fingolimod-treated multiple sclerosis patients

Mult Scler. 2015 May;21(6):726-34. doi: 10.1177/1352458514551456. Epub 2014 Nov 12.


Background: Fingolimod inhibits lymphocyte egress from lymphoid tissues, thus altering the composition of the peripheral lymphocyte pool of multiple sclerosis patients.

Objective: The objective of this paper is to evaluate whether fingolimod determines a decrease of newly produced T- and B-lymphocytes in the blood and a reduction in the T-cell receptor repertoire diversity that may affect immune surveillance.

Methods: Blood samples were obtained from multiple sclerosis patients before fingolimod therapy initiation and then after six and 12 months. Newly produced T and B lymphocytes were measured by quantifying T-cell receptor excision circles and K-deleting recombination excision circles by real-time PCR, while recent thymic emigrants, naive CD8(+) lymphocytes, immature and naive B cells were determined by immune phenotyping. T-cell receptor repertoire was analyzed by complementarity determining region 3 spectratyping.

Results: Newly produced T and B lymphocytes were significantly reduced in peripheral blood of fingolimod-treated patients. The decrease was particularly evident in the T-cell compartment. T-cell repertoire restrictions, already present before therapy, significantly increased after 12 months of treatment.

Conclusions: These results do not have direct clinical implications but they may be useful for further understanding the mode of action of this immunotherapy for multiple sclerosis patients.

Keywords: B-lymphocyte subsets; KRECs; Multiple sclerosis; T-cell receptor repertoire; T-lymphocyte subsets; TRECs; fingolimod; immunological monitoring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / drug effects*
  • Cell Proliferation* / drug effects
  • Female
  • Fingolimod Hydrochloride / pharmacology*
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Receptors, Antigen, T-Cell / drug effects*
  • T-Lymphocyte Subsets / drug effects*


  • Immunosuppressive Agents
  • Receptors, Antigen, T-Cell
  • Fingolimod Hydrochloride