RT Journal Article
SR Electronic
T1 Effect of Teriflunomide on Cells From Patients With Human T-cell Lymphotropic Virus Type 1–Associated Neurologic Disease
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e986
DO 10.1212/NXI.0000000000000986
VO 8
IS 3
A1 Enose-Akahata, Yoshimi
A1 Ngouth, Nyater
A1 Ohayon, Joan
A1 Mandel, Matt
A1 Chavin, Jeffrey
A1 Turner, Timothy J.
A1 Jacobson, Steven
YR 2021
UL http://nn.neurology.org/content/8/3/e986.abstract
AB Objective To test the hypothesis that teriflunomide can reduce ex vivo spontaneous proliferation of peripheral blood mononuclear cells (PBMCs) from patients with human T-cell lymphotropic virus type 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP).Methods PBMCs from patients with HAM/TSP were cultured in the presence and absence of teriflunomide and assessed for cell viability, lymphocyte proliferation, activation markers, HTLV-1 tax and HTLV-1 hbz messenger ribonucleic acid (mRNA) expression, and HTLV-1 Tax protein expression.Results In culture, teriflunomide did not affect cell viability. A concentration-dependent reduction in spontaneous proliferation of PBMCs was observed with 25 μM (38.3% inhibition), 50 μM (65.8% inhibition), and 100 μM (90.7% inhibition) teriflunomide. The inhibitory effects of teriflunomide were detected in both CD8+ and CD4+ T-cell subsets, which are involved in the immune response to HTLV-1 infection and the pathogenesis of HAM/TSP. There was no significant change in HTLV-1 proviral load (PVL) or tax mRNA/Tax protein expression in these short-term cultures, but there was a significant reduction of HTLV-1 PVL due to inhibition of proliferation of CD4+ T cells obtained from a subset of patients with HAM/TSP.Conclusions These results suggest that teriflunomide inhibits abnormal T-cell proliferation associated with HTLV-1 infection and may have potential as a therapeutic option in patients with HAM/TSP.CFSE=carboxyfluorescein succinimidyl ester; CMV=cytomegalovirus; EBV=Epstein-Barr virus; DHODH=dihydroorotate dehydrogenase; DNA=deoxyribonucleic acid; HD=healthy donor; HAM=HTLV-1–associated myelopathy; HTLV-1=human T-cell lymphotropic virus 1; HPRT=hypoxanthine phosphoribosyl transferase; IL=interleukin; mRNA=messenger ribonucleic acid; PBMC=peripheral blood mononuclear cell; PCR=polymerase chain reaction; PVL=proviral load; Th1=T helper 1; TSP=tropical spastic paraparesis