Medicity Research Laboratory and Department of Oral Pathology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland.
J Transl Med. 2014 Feb 13;12:44. doi: 10.1186/1479-5876-12-44.
Human papillomavirus (HPV) infection has traditionally been regarded as a sexually transmitted disease (STD), but recent evidence implicates that an infected mother can transmit HPV to her newborn during pregnancy, at delivery, perinatal period or later. Given the lack of any studies on HPV-specific immune responses in children, we conducted HPV16-specific cell-mediated immune (CMI) monitoring of the mother-child pairs with known oral and genital HPV follow-up (FU) data since the delivery. In the Finnish Family HPV Study, 10 out of 331 mothers developed incident cervical intraepithelial neoplasia (CIN) during their 14-year FU. Our hypothesis according to the common dogma is that there is no HPV16 specific immune response in offspring of the CIN mother as she/he has not started the sexual life yet.
We used overlapping 30-35 mer peptides covering the entire HPV16 E2, E6 and E7 protein sequences. Assays for lymphocyte proliferation capacity, cytokine production and HPV16-specific Foxp3 + CD25 + CD4+ regulatory T-cells were performed.
HPV16-specific proliferative T-cell responses were broader in children than in their mothers. Nine of 10 children had responses against both E2 peptide pools compared to only 4 of the 10 mothers. Six of the 10 children and only 2 mothers displayed reactivity to E6 and/or E7. The cytokine levels of IL-2 (p = 0.023) and IL-5 (p = 0.028) induced by all peptide pools, were also higher among children than their mothers. The children of the mothers with incident CIN3 had significantly higher IFN-γ (p = 0.032) and TNF-α (p = 0.008) levels than other children.
Our study is the first to show that also children could have HPV-specific immunity. These data indicate that the children have circulating HPV16-specific memory T-cells which might have been induced by previous HPV16 exposure or ongoing HPV 16 infection.
人乳头瘤病毒（HPV）感染传统上被认为是一种性传播疾病（STD），但最近的证据表明，感染的母亲在怀孕期间、分娩时、围产期或之后可以将 HPV 传染给新生儿。鉴于目前缺乏儿童 HPV 特异性免疫反应的相关研究，我们对已知有口腔和生殖器 HPV 随访（FU）数据的母婴对进行了 HPV16 特异性细胞介导免疫（CMI）监测。在芬兰家庭 HPV 研究中，331 名母亲中有 10 名在 14 年 FU 期间发生了宫颈上皮内瘤变（CIN）。根据普遍的观点，我们的假设是，由于 CIN 母亲的子女尚未开始性生活，因此他们的 HPV16 特异性免疫反应不存在。
我们使用了覆盖 HPV16 E2、E6 和 E7 蛋白序列全长的 30-35 mer 重叠肽。进行了淋巴细胞增殖能力、细胞因子产生和 HPV16 特异性 Foxp3+CD25+CD4+调节性 T 细胞的检测。
与母亲相比，儿童的 HPV16 特异性增殖性 T 细胞反应更为广泛。10 名儿童中有 9 名对两个 E2 肽池均有反应，而 10 名母亲中只有 4 名有反应。10 名儿童中有 6 名和仅 2 名母亲对 E6 和/或 E7 有反应。与母亲相比，所有肽池诱导的 IL-2（p=0.023）和 IL-5（p=0.028）的细胞因子水平也更高。患有 CIN3 的母亲的子女 IFN-γ（p=0.032）和 TNF-α（p=0.008）水平明显高于其他儿童。
本研究首次表明，儿童也可能具有 HPV 特异性免疫。这些数据表明，儿童具有循环的 HPV16 特异性记忆 T 细胞，这些细胞可能是由先前的 HPV16 暴露或持续的 HPV16 感染引起的。
