BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1), also denominated Human T-cell leukemia virus-1, induces immune activation and secretion of proinflammatory cytokines, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Regulatory T lymphocytes (Tregs) may control of inflammation through the production of regulatory cytokines, including IL10 and TGF-β. In this study we determined the frequencies of CD4 + and CD8 + Tregs in a HAM/TSP population, compared to asymptomatic carriers and uninfected individuals, as well as investigated the profiles of regulatory and inflammatory cytokines.
METHODS: Asymptomatic HTLV-1 carriers and HAM/TSP patients were matched by sex and age. The frequencies of IL10- and/or TGF-β-producing Tregs were quantified by flow cytometry. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to quantify HTLV-1 proviral load and the mRNA expression of cytokines and cellular receptors in peripheral blood mononuclear cells.
RESULTS: Total frequencies of CD4 + Tregs, as well as the IL10-producing CD4 + and CD8 + Treg subsets, were statistically higher in patients with HAM/TSP compared to asymptomatic HTLV-1-infected individuals. In addition, a positive correlation was found between the frequency of CD4 + IL10 + Tregs and proviral load in the HAM/TSP patients evaluated. A positive correlation was also observed between gene expression of proinflammatory versus regulatory cytokines only in HAM / TSP group.
CONCLUSIONS: A higher frequencies of IL10-producing Tregs were identified in patients with HAM/TSP. Imbalanced production of IL10 in relation to TGF-β may contribute to the increased inflammatory response characteristically seen in HAM/TSP patients.

The Human T-cell leukemia virus type-I (HTLV-1) is the causal agent of HTLV-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HAM/TSP is the result of demyelination and cell death in the spinal cord and disruption of the blood-brain barrier (BBB), mediated by a virus-induced inflammatory response. In this study, we applied Positron Emission Tomography with 18F-fluordeoxyglucose (18F-FDG PET) to evaluate brain metabolism in a group of 47 patients infected with HTLV-1, and 18 healthy controls. Patients were divided into three groups according to their neurological symptoms. A machine learning (ML) based Gaussian Processes classification algorithm (GPC) was applied to classify between patient groups and controls and also to organize the three patient groups, based on gray and white matter brain metabolism. We found that GPC was able to differentiate the HAM/TSP group from controls with 85% accuracy (p = 0.003) and the asymptomatic seropositive patients from controls with 85.7% accuracy (p = 0.001). The weight map suggests diffuse cortical hypometabolism in both patient groups when compared to controls. We also found that the GPC could separate the asymptomatic HTLV-1 patients from the HAM/TSP patients, but with a lower accuracy (72.7%, p = 0.026). The weight map suggests a diffuse pattern of lower metabolism in the asymptomatic group when compared to the HAM/TSP group. These results are compatible with distinctive patterns of glucose uptake into the brain of HTLV-1 patients, including those without neurological symptoms, which differentiate them from controls. Furthermore, our results might unveil surprising aspects of the pathophysiology of HAM/TSP and related diseases, as well as new therapeutic strategies.