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May 2021; 8 (3) ArticleOpen Access

Effect of Teriflunomide on Cells From Patients With Human T-cell Lymphotropic Virus Type 1–Associated Neurologic Disease

Yoshimi Enose-Akahata, Nyater Ngouth, Joan Ohayon, Matt Mandel, Jeffrey Chavin, Timothy J. Turner, Steven Jacobson
First published April 9, 2021, DOI: https://doi.org/10.1212/NXI.0000000000000986
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  • Figure 1
    Figure 1 Inhibition of Spontaneous Lymphoproliferation With Teriflunomide

    (A) Cell viability of PBMCs of an HD cultured with teriflunomide. (B) Spontaneous lymphoproliferation in cultured PBMCs of an HD (left graph) and a patient with HAM/TSP (HAM 1; right graph) with defined concentrations of teriflunomide. (C) Inhibition of spontaneous lymphoproliferation in cultured PBMCs of 12 patients with HAM/TSP with defined concentrations of teriflunomide. Each data point represents the mean of 3H incorporation in a total of 12 patients with HAM/TSP. (D) Concentration-dependent inhibitory effect of teriflunomide on spontaneous lymphoproliferation in cultured PBMCs of 12 patients with HAM/TSP at day 5. Each data point represents the mean with standard deviation. (E) Percent change of spontaneous lymphoproliferation in cultured PBMCs of 12 patients with HAM/TSP with teriflunomide compared with those without teriflunomide at day 5. Each bar represents the mean with SD.

  • Figure 2
    Figure 2 Inhibition of CD8+ and CD4+ T-Cell Proliferation With Teriflunomide

    (A) Representative dot plots of CFSE staining in CD8+ and CD4+ T cells of a patient with HAM/TSP (HAM 1) with defined concentrations of teriflunomide after culture for 5 days. (B) Inhibitory effect of teriflunomide on CD8+ T-cell proliferation in cultured PBMCs of 12 patients with HAM/TSP at day 5. Each data point represents the mean of CFSE staining with SD. (C) Percent change of CD8+ T-cell proliferation in cultured PBMCs of 12 patients with HAM/TSP with teriflunomide compared with those without teriflunomide at day 5. Each bar represents the mean with SD. (D) Inhibitory effect of teriflunomide on CD4+ T-cell proliferation in cultured PBMCs of 12 patients with HAM/TSP at day 5. Each data point represents the mean of CFSE staining with SD. (E) Percent change of CD4+ T-cell proliferation in cultured PBMCs of 12 patients with HAM/TSP with teriflunomide compared with those without teriflunomide at day 5. Each bar represents the mean with SD. HAM = HTLV-1–associated myelopathy; PBMC = peripheral blood mononuclear cell; TSP = tropical spastic paraparesis.

  • Figure 3
    Figure 3 Teriflunomide Did Not Change Activation Marker of Patients With HAM/TSP

    Frequency of CD25+ cells in the CD4+ T-cell population (A) and in the CD8+ T-cell population (B) of PBMCs from 9 randomly selected patients with HAM/TSP cultured with defined concentrations of teriflunomide. HAM = HTLV-1–associated myelopathy; PBMC = peripheral blood mononuclear cell; TSP = tropical spastic paraparesis.

  • Figure 4
    Figure 4 HTLV-1 PVL and mRNA Expression in Cultured PBMCs of Patients With HAM/TSP With Teriflunomide

    (A) Inhibition of HTLV-1 PVL in cultured PBMCs of 6 randomly selected patients with HAM/TSP with defined concentrations of teriflunomide. Each data point represents the mean of HTLV-1 PVL in a total of 6 patients with HAM/TSP. Shaded area represents the range of SD based on HTLV-1 PVL of total 6 patients with HAM/TSP at day 0. (B) Inhibitory effect of teriflunomide on HTLV-1 PVL in cultured PBMCs of 6 patients with HAM/TSP (patient numbers are indicated) at day 5. (C) Percent change of HTLV-1 PVL in cultured PBMCs of 6 patients with HAM/TSP with teriflunomide compared with those without teriflunomide at day 5. Each bar represents the mean with SD. (D) HTLV-1 tax mRNA expression in PBMCs of 6 patients with HAM/TSP cultured with defined concentrations of teriflunomide for 20 hours. (E) HTLV-1 hbz mRNA expression in PBMCs of 6 patients with HAM/TSP cultured with defined concentrations of teriflunomide for 20 hours. (F) HTLV-1 Tax protein expression in CD4+ T cells of cultured PBMCs from 12 patients with HAM/TSP with defined concentrations of teriflunomide for 20 hours. HAM = HTLV-1–associated myelopathy; HTLV-1 = human T-cell lymphotropic virus 1; PBMC = peripheral blood mononuclear cell; PVL = proviral load; TSP = tropical spastic paraparesis.

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