Ghezeldasht Sanaz Ahmadi, Sadeghian Hamed, Azarpazhooh Mahmoud Reza, Shamsian Seyyed Ali Akbar, Rafatpanah Houshang, Mahmoodi Mahmood, Rezaee Seyyed Abdolrahim
Research Center for HIV/AIDS, HTLV and Viral Hepatitis, Iranian Academic Center for Education, Culture & Research (ACECR), Mashhad Branch, Mashhad, Iran.
Immunology Research Center, Inflammation and Inflammatory Diseases Division, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Appl Biochem Biotechnol. 2017 Aug;182(4):1403-1414. doi: 10.1007/s12010-017-2406-7. Epub 2017 Jan 18.
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an aggressive neurological disease. The CD4CD25 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 CD4CD25 cell counts had no significant differences between HAM/TSP and ACs. Findings revealed a higher PVL in HAM/TSPs (313.36 copies/10) compared to ACs (144.93 copies/10, 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 CD4CD25 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.
人类嗜T淋巴细胞病毒1型相关脊髓病/热带痉挛性截瘫（HAM/TSP）是一种侵袭性神经疾病。CD4CD25 T细胞群体在维持免疫耐受和预防此类自身免疫性疾病中起关键作用。在本研究中，使用实时聚合酶链反应（PCR）、TaqMan方法和流式细胞术检测了21例HAM/TSP患者和16例人类嗜T淋巴细胞病毒1型健康携带者（ACs）的前病毒载量（PVL）、叉头框蛋白p3（Foxp3）、糖皮质激素诱导的肿瘤坏死因子受体相关蛋白（GITR）基因表达以及调节性T细胞（Tregs）计数。通过清单和小见运动残疾评分（OMDS）评估人口统计学、疾病史和脊髓病严重程度。HAM/TSP的平均OMDS为4.82±2.37，与Tregs计数或Foxp3、GITR和PVL的表达无显著相关性。HAM/TSP和ACs之间的CD4CD25细胞计数无显著差异。研究结果显示，与ACs（144.93拷贝/10，p = 0.035）相比，HAM/TSP患者的PVL更高（313.36拷贝/10）。HAM/TSP患者的Foxp3和GITR mRNA水平（分别为11.78和13.80）低于健康携带者（分别为18.44和21.00，p分别为0.041和0.03）。在HAM/TSP患者中，Tregs频率与Foxp3基因表达（R = 0.67，p = 0.006）以及GITR和Foxp3（R = 0.84，p = 0.042）之间存在显著相关性。此外，转录因子与CD4CD25 T细胞频率有很强的相关性。这些发现表明，人类嗜T淋巴细胞病毒1型感染可改变主要功能转录因子FOXP3和GITR的表达，这可能导致Tregs的免疫反应恶化，进而导致HAM/TSP的表现。
