PD‐1 and TIM‐3 Expression on Peripheral Blood T Cells in HTLV‐1‐Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) and Their Correlations With Disease Stage and Proviral Load

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.