T helper type 9 cell response and its role in the neurological clinic of patients with Human T-lymphotropic virus 1.

Human T-lymphotropic virus 1 (HTLV-1) affects 5-10 million individuals worldwide. Most of those infected with this virus remain asymptomatic; however, 0.25%-4% of individuals develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), while 2%-4% develop adult T-cell leukemia/lymphoma (ATLL). Understanding the immune response inherent in this infection is extremely important. The role of T helper type 1 (Th1) and Th2 cells in HTLV-1 infection is well known; however, exploring the different subtypes of immune responses is also necessary. The role of Th9 cells in HTLV-1 infection and the mechanisms involved in their interference in the pathophysiological process of HAM/TSP is poorly understood. This study aimed to evaluate the expression profiles of PU.1, interferon regulatory factor 4 (IRF-4), and cytokine interleukin-9 (IL-9) during the induction of peripheral immune response and their role in the HTLV-1-infected patients' neurological symptoms. This analytical cross-sectional study was carried out at the Laboratory of Clinical and Epidemiology of Endemic Diseases and the Laboratory of Immunopathology, both from the Tropical Medicine Center at the Federal University of Pará. Assessment of neurological parameters was performed (gait, Expanded Kurtzke Disability State Scale (EDSS) score, upper and lower limb reflexes, Hoffman's sign, Babinski reflex, and clonus reflex). For Th9 cell analysis, peripheral blood samples were collected from HTLV-1-infected patients; then, the lymphomononuclear cells were separated followed by the isolation of messenger ribonucleic acid (mRNA). Complementary deoxyribonucleic acid (cDNA) synthesis each sample was carried out. The gene expression levels of PU.1, IRF-4, and IL-9 as well as those of constitutive genes (glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and β-actin) were quantified by real-time polymerase chain reaction (qPCR). This study included 81 HTLV-1-infected patients, of whom 47 were asymptomatic, 13 were mono/oligosymptomatic (MOS), and 21 developed HAM/TSP. IL-9 was the least expressed gene among the three studied groups. The MOS group showed the lowest expression levels of PU.1, IRF-4, and IL-9. HAM/TSP patients showed lower IL-9 protein quantification. Negative correlations were found between IL and 9 and EDSS in MOS patients and between PU.1, EDSS, IRF-4, and EDSS in the HAM/TSP group. An association was found between IL and 9 and Babinski reflex in the HAM/TSP group, suggesting that this gene was more highly expressed in patients who did not have this pathological sign. Th9 cells may interfere with the neurological progression of HAM/TSP and act as a protective factor.