title: 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.
abstract: 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.
authors: Hanna-Mari
authors: HM
authors: Koskimaa
authors: Anna E
authors: AE
authors: Paaso
authors: Marij J P
authors: MJ
authors: Welters
authors: Seija E
authors: SE
authors: Grénman
authors: Kari J
authors: KJ
authors: Syrjänen
authors: Sjoerd H
authors: SH
authors: van der Burg
authors: Medicity Research Laboratory and Department of Oral Pathology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland. stina.syrjanen@utu.fi.
authors: Stina M
authors: SM
authors: Syrjänen
mesh_terms: D049109:Cell Proliferation; D002648:Child; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D005190:Family; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D009035:Mothers; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D010455:Peptides; D014764:Viral Proteins