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 (T H ) cells T H 1, T H 2, T H 17, and peripheral regulatory T cell (pT reg ) 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 T H 1 cells were decreased, whereas those of T H 2 cells were increased and those of T H 17 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 pT reg 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 T H 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 T H 1-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.