Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients

Mult Scler. 2016 Jul;22(8):1061-1070. doi: 10.1177/1352458515608961. Epub 2015 Oct 12.


Background: Dimethyl fumarate (DMF) alters the phenotype of circulating immune cells and causes lymphopenia in a subpopulation of treated multiple sclerosis (MS) patients.

Objective: To phenotypically characterize circulating leukocytes in DMF-treated MS patients.

Methods: Cross-sectional observational comparisons of peripheral blood from DMF-treated MS patients (n = 17 lymphopenic and n = 24 non-lymphopenic), untreated MS patients (n = 17) and healthy controls (n = 23); immunophenotyped using flow cytometry. Longitudinal samples were analyzed for 13 DMF-treated patients.

Results: Lymphopenic DMF-treated patients had significantly fewer circulating CD8(+) and CD4(+) T cells, CD56(dim) natural killer (NK) cells, CD19(+) B cells and plasmacytoid dendritic cells when compared to controls. CXCR3(+) and CCR6(+) expression was disproportionately reduced among CD4(+) T cells, while the proportion of T-regulatory (T-reg) cells was unchanged. DMF did not affect circulating CD56(hi) NKcells, monocytes or myeloid dendritic cells. Whether lymphopenic or not, DMF-treated patients had a lower proportion of circulating central and effector memory T cells and concomitant expansion of naïve T cells compared to the controls.

Conclusions: DMF shifts the immunophenotypes of circulating T cells, causing a reduction of memory cells and a relative expansion of naïve cells, regardless of the absolute lymphocyte count. This may represent one mechanism of action of the drug. Lymphopenic patients had a disproportionate loss of CD8(+) T-cells, which may affect their immunocompetence.

Keywords: Dimethyl fumarate; immunocompetence; immunology; lymphocyte types; lymphopenia; memory T cells; multiple sclerosis; neuroimmunology; relapse.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Case-Control Studies
  • Cross-Sectional Studies
  • Dimethyl Fumarate / adverse effects
  • Dimethyl Fumarate / therapeutic use*
  • Flow Cytometry
  • Humans
  • Immunologic Memory / drug effects*
  • Immunophenotyping / methods
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Lymphocyte Count
  • Lymphopenia / chemically induced
  • Lymphopenia / immunology
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Phenotype
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Time Factors
  • Treatment Outcome


  • Immunosuppressive Agents
  • Dimethyl Fumarate