Dimethyl fumarate treatment alters circulating T helper cell subsets in multiple sclerosis

OBJECTIVE To evaluate the effect of dimethyl fumarate (DMF; Tecfidera, Biogen, Weston, MA) on CD4(+) and CD8(+) T cell subsets in patients with multiple sclerosis (MS). METHODS Peripheral lymphocyte subsets, including CD4(+) and CD8(+) memory cells and T helper (TH) cells TH1, TH2, TH17, and peripheral regulatory T cell (pTreg) subpopulations were analyzed before and 6 months after onset of DMF treatment. RESULTS CD4(+) and CD8(+) memory T cells were preferentially decreased compared to naive CD4(+) and CD8(+) T cell populations. Within the CD4(+) memory T cell population, frequencies of TH1 cells were decreased, whereas those of TH2 cells were increased and those of TH17 cells remained unaltered. Accordingly, we observed decreased production of interferon γ, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α, and interleukin (IL)-22 by CD4(+) T cells under DMF treatment, whereas the frequency of IL-4- and IL-17A-producing CD4(+) T cells remained unchanged. With regard to regulatory T cells, proportions of pTreg increased following DMF treatment. CONCLUSION Our data demonstrate that DMF treatment of patients with MS affects predominantly memory T cells accompanied by a shift in TH cell populations, resulting in a shift toward anti-inflammatory responses. These findings indicate that monitoring of memory subsets might enhance vigilance of impaired antiviral immunity and that patients with TH1-driven disease might preferentially benefit from DMF treatment. CLASSIFICATION OF EVIDENCE This study provides Class IV evidence that DMF might preferentially reduce CD4(+) and CD8(+) memory T cells in MS.