Evaluation of T Regulatory Lymphocytes Transcription Factors in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Patients

• Published in: Applied biochemistry and biotechnology 2017-08, Vol.182 (4), p.1403-1414
• Main Authors: Ghezeldasht, Sanaz Ahmadi, Sadeghian, Hamed, Azarpazhooh, Mahmoud Reza, Shamsian, Seyyed Ali Akbar, Rafatpanah, Houshang, Mahmoodi, Mahmood, Rezaee, Seyyed Abdolrahim
• Format: Article
• Language: English
• Subjects: Adult; Attitude control; Autoimmune diseases; Biochemistry; Biotechnology; Case-Control Studies; CD25 antigen; CD4 antigen; Cell Count; Central nervous system diseases; Chemistry; Chemistry and Materials Science; Correlation; Current carriers; Cytometry; Demographics; Female; Flow cytometry; Forkhead protein; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Foxp3 protein; Gene expression; Glucocorticoid-Induced TNFR-Related Protein - genetics; Glucocorticoid-Induced TNFR-Related Protein - metabolism; Glucocorticoids; Hereditary spastic paraplegia; Human T-lymphotropic virus 1 - physiology; Humans; Immune response; Immune system; Immunological tolerance; Immunology; Immunoregulation; Lymphocytes; Lymphocytes T; Male; Middle Aged; Motor task performance; Neurology; Paraparesis, Tropical Spastic - genetics; Paraparesis, Tropical Spastic - immunology; Paraparesis, Tropical Spastic - metabolism; Patients; Polymerase chain reaction; Spasticity; Spinal cord; T cell receptors; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - metabolism; Time measurement; Transcription factors; Tropical spastic paraparesis; Viral Load
• ISSN: 0273-2289; 1559-0291
• DOI: 10.1007/s12010-017-2406-7

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an aggressive neurological disease. The CD4 + CD25 + T cell population plays pivotal roles in the maintenance of immunological tolerance and prevention of such autoimmune diseases. In the current study, proviral load (PVL), factor forkhead box p3 ( Foxp3) , and glucocorticoid-induced tumor necrosis factor receptor-related protein ( GITR) gene expression and regulatory T cells (Tregs) counts of 21 HAM/TSP patients and 16 HTLV-1 healthy carriers (ACs) were measured using real-time PCR, TaqMan method, and flow cytometry. The demographic, history of disease, and severity of myelopathy were assessed by a checklist and the Osame motor disability score (OMDS). The mean OMDS for HAM/TSP was 4.82 ± 2.37 which had no significant correlation with Treg count or the expression of Foxp3 , GITR , and PVL. The CD4 + CD25 + cell counts had no significant differences between HAM/TSP and ACs. Findings revealed a higher PVL in HAM/TSPs (313.36 copies/10 4 ) compared to ACs (144.93 copies/10 4 , p  = 0.035). The Foxp3 and GITR mRNA levels were lower in HAM/TSP patients (11.78 and 13.80, respectively) than those in healthy carriers (18.44 and 21.00, p  = 0.041 and 0.03, respectively). There was a significant correlation between Treg frequency and Foxp3 gene expression ( R  = 0.67, p  = 0.006) and GITR and Foxp3 ( R  = 0.84, p  = 0.042) in HAM/TSP patients. Furthermore, the transcription factors have strong correlations with CD4 + CD25 + T cell frequencies. These findings suggest that HTLV-1 infection can modify the expression of main functional transcription factors, FOXP3 and GITR , which may lead to immune response deterioration of Tregs and consequently HAM/TSP manifestation.