PD-1 and TIM-3 Expression on Peripheral Blood T Cells in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis...

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a long-term neuroinflammatory condition without effective therapy, partly due to limited understanding of its immunopathogenesis. Although higher HTLV-1 proviral load (PVL) is linked to disease susceptibility, the contribution of T-cell immune checkpoints remains unclear. PD-1 and TIM-3 regulate T-cell function, and evaluating them alongside cytokine balance may provide insight into disease mechanisms. This study included 30 HAM/TSP patients, 30 HTLV-1 asymptomatic carriers, and 30 healthy controls. Distribution of PD-1 and TIM-3 across CD4⁺ and CD8⁺ T cells was assessed by flow cytometry, serum IFN-γ and IL-10 concentrations were quantified by ELISA, HTLV-1 proviral load quantification was performed using a SYBR Green-based qPCR assay designed and validated in this study and viral subtypes were determined by LTR sequencing and drawing phylogenetic tree. Although CD4⁺ and CD8⁺ T cells from HAM/TSP cases displayed elevated PD-1 expression, TIM-3 expression was similar across groups. IFN-γ, but not IL-10, was elevated in HAM/TSP. Increased PD-1⁺CD8⁺ T-cell frequency and IFN-γ levels were associated with proviral load, motor disability, and disease duration. Elevated PD-1 expression without concurrent TIM-3 upregulation, together with high IFN-γ levels, suggests a proinflammatory immune profile in HAM/TSP rather than classical T-cell exhaustion.