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Enhanced T-cell maturation and monocyte aggregation are features of cellular inflammation in human T-lymphotropic virus type-1-associated myelopathy.
Clinical Infectious Diseases ( IF 8.2 ) Pub Date : 2019-05-08 , DOI: 10.1093/cid/ciz369
Zainab Saeed 1 , Aileen Rowan 1 , Claire Greiller 1 , Graham P Taylor 1 , Katrina M Pollock 1
Affiliation  

BACKGROUND Human T-lymphotropic virus type-1 (HTLV-1) associated myelopathy (HAM), is an inflammatory condition characterised by severe disability and high levels of infected white blood cells. The circulating cellular inflammatory changes that distinguish this condition from asymptomatic infection are not well understood. METHODS To investigate the immune characteristics of individuals with low or high HTLV-1 proviral load (pVL), symptomatic disease and the impact of immunosuppressive therapy, thirty-eight women living with HTLV-1 infection, with a median age 59 (52-68) years were studied. Nineteen were asymptomatic carriers, with low or high pVL, and nineteen were diagnosed with HAM, with ten receiving anti-inflammatory therapy. Peripheral blood mononuclear cells were stained and analysed for frequency distribution and activation of innate and adaptive immune cell subsets using multi-parameter flow cytometry. RESULTS Inflation of the CD4:CD8 ratio (>2) was observed amongst all groups irrespective of pVL. The frequency of naïve CD4+ T-cells correlated inversely with HTLV-1 pVL (rs=-0.344, p=0.026). Mature TEM CD4+ T-cells were expanded in patients with untreated HAM compared with asymptomatic carriers (p<0.001), but less so in those on therapy. High levels of exhausted (PD-1+) and senescent (CD28null) CD4+ and CD8+ T-cells were observed in all individuals particularly in those with HAM, whilst monocytes showed increased aggregation, and CD14+CD56- monocytes were less frequent. CONCLUSIONS CD4:CD8 ratio inflation is a feature of HTLV-1 infection, whereas enhanced CD4+ T-cell maturation and monocyte aggregation are features of HAM reflecting widespread inflammatory change, which may be detectable pre-symptomatically, and be amenable to anti-inflammatory treatment.

中文翻译:

增强的T细胞成熟和单核细胞聚集是人类T淋巴病毒1型相关性脊髓病中细胞炎症的特征。

背景技术人类1型T淋巴细胞病毒(HTLV-1)相关的脊髓病(HAM)是一种炎症性疾病,其特征在于严重的残疾和高水平的感染白细胞。尚不清楚将这种状况与无症状感染区分开的循环性细胞炎性变化。方法调查38名HTLV-1感染妇女,中位年龄为59岁(52-68岁)的低或高HTLV-1前病毒载量(pVL),症状性疾病和免疫抑制疗法的影响,这些患者的免疫特性)年进行了研究。19例是无症状携带者,pVL值较低或较高; 19例被诊断为HAM,其中10例接受抗炎治疗。对外周血单核细胞进行染色,并使用多参数流式细胞仪分析先天和适应性免疫细胞亚群的频率分布和激活。结果在所有组中均观察到CD4:CD8比(> 2)的膨胀,而与pVL无关。幼稚的CD4 + T细胞的频率与HTLV-1 pVL成反比(rs = -0.344,p = 0.026)。与无症状携带者相比,未经治疗的HAM患者中成熟的TEM CD4 + T细胞得以扩增(p <0.001),而接受治疗的患者则更少。在所有个体中,尤其是在患有HAM的个体中,均观察到高水平的精疲力竭(PD-1 +)和衰老(CD28null)CD4 +和CD8 + T细胞,而单核细胞显示增加的聚集,而CD14 + CD56-单核细胞的频率降低。结论CD4:CD8比值膨胀是HTLV-1感染的特征,
更新日期:2020-03-19
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