Human papillomavirus 16-specific cell-mediated immunity in children born to mothers with incident cervical intraepithelial neoplasia (CIN) and to those constantly HPV negative

Journal of Translational Medicine

Research

Marij J. P. Welters¹  Sjoerd H. van der Burg¹  Kari Syrjänen²  Seija Grénman³  Hanna-Mari Koskimaa⁴  Anna Paaso⁴  Stina Syrjänen⁴ 

[1] Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands;Department of Clinical Research, Biohit Oyj, Helsinki, Finland;Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland;Medicity Research Laboratory and Department of Oral Pathology, Faculty of Medicine, Institute of Dentistry, University of Turku, Lemminkäisenkatu 2, 20540, Turku, Finland;

关键词: Cell-mediated immunity;    Children;    Cytokine secretion;    Human papillomavirus;    Peripheral blood mononuclear cell;    Serological antibody;    T-cell immunity;   

DOI  :  10.1186/s12967-015-0733-4

 received in 2015-06-25, accepted in 2015-11-18,  发布年份 2015

来源: Springer

【 摘 要 】

ObjectivesHPV infections are detected in sexually naive children. This has raised the question about the role of early HPV infections in either protecting or predisposing to further HPV infections. HPV16-specific cell-mediated immunity (CMI) was studied in 10 case-children born to mothers with an incident cervical intraepithelial neoplasia (CIN) diagnosed during their 14-year follow-up (FU), and in 21 children born to mothers, who remained constantly HPV-negative (controls). The mean age of children was 12.3 years.MethodsPeripheral blood mononuclear cells were isolated from blood and stimulated with peptide pools covering HPV16 E2, E6 and E7. Proliferation of lymphocytes, their secretion of cytokines, and the frequency of regulatory T-cells were determined. The results were correlated with the HPV status and analyzed in a nested case–control setting.ResultsAll children, except two controls, displayed CMI against HPV16 E2, E6 and/or E7 peptides associated with type 1 and 2 cytokine secretion. Only two statistically significant differences were found in the nested case–control setting; (1) case-children had a higher TNF-α response to HPV16 E2 (p = 0.004) than controls and (2) controls had no response to HPV16 E7.2 peptide pool while 3/10 case-children had (p = 0.013). Totally, 50 and 57 % of the cases and controls, respectively, had HPV positive oral samples at some FU-visit. In addition, the children without any HPV antibodies before the age of 6 months showed proliferative responses of PBMC after HPV16 exposure more frequently than other children (p = 0.045).ConclusionsHPV16-specific CMI is common in young, sexually inexperienced children. This suggests that oral HPV infections occur frequently in children. Our results might also explain the previous findings that half of healthy adults demonstrate HPV-specific CMI irrespective of their partner/sexual status.

【 授权许可】

CC BY   
© Koskimaa et al. 2015