Human papillomavirus 16 E2-, E6- and E7-specific T-cell responses in children and their mothers who developed incident cervical intraepithelial neoplasia during a 14-year follow-up of the Finnish Family HPV cohort

Journal of Translational Medicine

Stina M Syrjänen¹  Sjoerd H van der Burg⁴  Kari J Syrjänen³  Seija E Grénman²  Marij JP Welters⁴  Anna E Paaso¹  Hanna-Mari Koskimaa¹ 

[1] Medicity Research Laboratory and Department of Oral Pathology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland;Department of Obstetrics and Gynaecology, Turku University Hospital, Turku, Finland;Teaching and Research Institute, Barretos Cancer Hospital, Barretos-SP, Brazil;Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands

关键词: Mothers;    Children;    Cytokines;    T-cell immunity;    HPV16;   

Others  :  817948
DOI  :  10.1186/1479-5876-12-44

 received in 2013-10-09, accepted in 2014-01-14,  发布年份 2014

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2014 Koskimaa et al.; licensee BioMed Central Ltd.

【 图 表 】

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