Schwarz Christine M, Strenger Volker, Strohmaier Heimo, Singer Georg, Kaiser Margarita, Raicht Andrea, Schwinger Wolfgang, Urban Christian
Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
Center for Medical Research (ZMF), Core Facility Flow Cytometry, Medical University of Graz, Graz, Austria.
Front Pediatr. 2018 Jul 2;6:191. doi: 10.3389/fped.2018.00191. eCollection 2018.
Primary infection with human herpes virus 6 (mainly HHV-6B) commonly occurs in the first 2 years of life leading to persistence and the possibility of virus reactivation later in life. Consequently, a specific cellular immune response is essential for effective control of virus reactivation. We have studied cell-mediated immune response to HHV-6 (U54) in healthy children and adolescents. By flow cytometry, the amount of cytokine (interferon gamma-IFN- γ, interleukin 2-IL-2, tumor necrosis factor alpha-TNF-α) secreting T-cells were measured after 10 days of pre-sensitization and 6 h of re-stimulation with mixtures of pooled overlapping peptides from U54, staphylococcal enterotoxin B (SEB, positive control), or Actin (negative control) in healthy children and adolescents without any underlying immune disorder or infectious disease. All individuals showed a virus-specific response for at least one cytokine in either CD4+ or CD8+ cells. Percentages of individuals with HHV-6-specific TNF-α response in CD4+ (48% of individuals) as well as CD8+ (56% of individuals) were always the highest. Our data show significantly higher frequencies of HHV-6-specific TNF-α producing CD8+ T-cells in individuals older than 10 years of life ( = 0.033). Additionally, the frequency of HHV-6 specific TNF-α producing CD8+ T-cells positively correlated with the age of the individuals. Linear regression analysis showed a positive relation between age and frequency of HHV-6-specific TNF-α producing CD8+ T-cells. Results indicate that T-cell immune response against HHV-6 is commonly detectable in healthy children and adolescents with higher frequencies of antigen-specific T-cells in older children and adolescents possibly reflecting repeated stimulation by viral persistence and subclinical reactivation.
人疱疹病毒6型（主要是HHV-6B）的初次感染通常发生在生命的头2年，导致病毒持续存在，并有可能在日后重新激活。因此，特异性细胞免疫反应对于有效控制病毒重新激活至关重要。我们研究了健康儿童和青少年对HHV-6（U54）的细胞介导免疫反应。通过流式细胞术，在无任何潜在免疫疾病或传染病的健康儿童和青少年中，用来自U54的重叠肽混合物、葡萄球菌肠毒素B（SEB，阳性对照）或肌动蛋白（阴性对照）进行预致敏10天和再刺激6小时后，测量分泌细胞因子（干扰素γ-IFN-γ、白细胞介素2-IL-2、肿瘤坏死因子α-TNF-α）的T细胞数量。所有个体在CD4+或CD8+细胞中对至少一种细胞因子表现出病毒特异性反应。CD4+（48%的个体）以及CD8+（56%的个体）中具有HHV-6特异性TNF-α反应的个体百分比始终最高。我们的数据显示，10岁以上个体中产生HHV-6特异性TNF-α的CD8+T细胞频率显著更高（P = 0.033）。此外，产生HHV-6特异性TNF-α的CD8+T细胞频率与个体年龄呈正相关。线性回归分析显示年龄与产生HHV-6特异性TNF-α的CD8+T细胞频率之间存在正相关关系。结果表明，在健康儿童和青少年中通常可检测到针对HHV-6的T细胞免疫反应，年龄较大的儿童和青少年中抗原特异性T细胞频率更高，这可能反映了病毒持续存在和亚临床再激活的反复刺激。
