研究动态
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T helper 9细胞的反应及其在患有人类T细胞淋巴病毒1的患者神经学诊断中的作用。

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

发表日期:2023 Aug 25
作者: Roberto de Sena Rodrigues Júnior, Jéssica Antonia Nunes Gomes, George Alberto da Silva Dias, Satomi Fujihara, Gilberto Toshimitsu Yoshikawa, Roberta Vilela Lopes Koyama, Rita Catarina Medeiros Sousa, Juarez Antonio Simões Quaresma, Hellen Thais Fuzii
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

人类T淋巴病毒1型(HTLV-1)全球感染人数为500-1000万。绝大多数感染者无症状,但0.25%-4%的人会出现HTLV-1相关的脊髓病/热带痉挛性截瘫(HAM/TSP),而2%-4%的人会发展成成人T细胞白血病/淋巴瘤(ATLL)。了解这种感染中固有的免疫反应非常重要。T辅助细胞1(Th1)和Th2细胞在HTLV-1感染中的作用已经很清楚,但也需要探索不同亚型的免疫反应。Th9细胞在HTLV-1感染中的作用以及其对HAM/TSP病理过程干扰的机制尚不明确。本研究旨在评估PU.1、干扰素调节因子4(IRF-4)和细胞因子白细胞介素-9(IL-9)在外周免疫反应诱导过程中的表达谱,并评估它们在HTLV-1感染患者神经症状中的作用。本分析性横断面研究在巴拉州联邦大学热带医学中心的传染病临床和流行病学实验室以及免疫病理实验室进行。对神经学参数进行评估(步态、扩大的Kurtzke残疾状态评分(EDSS),上肢和下肢反射,Hoffman征,Babinski征和强直反射)。为了进行Th9细胞分析,从HTLV-1感染者处收集外周血样本,然后分离淋巴单核细胞并提取信使核糖核酸(mRNA)。对每个样本进行互补脱氧核糖核酸(cDNA)合成。通过实时聚合酶链反应(qPCR)定量PU.1、IRF-4和IL-9的基因表达水平以及构成性基因(糖酵解产物3-磷酸脱氢酶(GAPDH)和β-actin)。本研究包括81名HTLV-1感染者,其中47名无症状,13名单/少症状(MOS)患者,以及21名发展成HAM/TSP的患者。IL-9是三个研究组中表达最低的基因。MOS组显示了最低的PU.1、IRF-4和IL-9表达水平。HAM/TSP患者显示了较低的IL-9蛋白定量。在MOS患者中,IL-9与EDSS呈负相关,在HAM/TSP组中PU.1与EDSS、IRF-4与EDSS呈负相关。在HAM/TSP组中,IL-9与Babinski征之间存在关联,提示在没有此病理征象的患者中这一基因的表达更高。Th9细胞可能干扰HAM/TSP的神经病变进展,并起到一种保护因子的作用。版权所有© 2023 Elsevier GmbH。保留所有权利。
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.Copyright © 2023 Elsevier GmbH. All rights reserved.