title: Cell mediated immunity against HPV16 E2, E6 and E7 peptides in women with incident CIN and in constantly HPV-negative women followed-up for 10-years.
abstract: BACKGROUND
  Virus-specific cell-mediated immunity (CMI) plays a role in the outcome of genital HPV infections. To cast further light on the question why most women clear their HPV infection while others develop high-grade cervical intraepithelial neoplasia (CIN), we analyzed HPV16 E2-, E6- and E7 -specific CMI in women who developed CIN during a 10-year follow-up of the Finnish Family HPV cohort.
  
  
  METHODS
  Overlapping 30-35 mer peptides covering the entire HPV16 E2-, E6- and E7 protein sequences were used for defining the lymphocyte proliferation capacity, cytokine production (IL-2, IL-5, IL-10, IL-17A, IFN-γ and TNF-α) and numbers of HPV16 -specific CD4+ CD25+ Foxp3+ regulatory T-cells in 10 women who developed CIN, and in 22 control women who tested constantly HPV-negative during the follow-up. HPV-specific CMI was related to the demographic data including sexual behavior, smoking and alcohol consumption.
  
  
  RESULTS
  Women with CIN and their controls had similar T-cell mediated immunity against HPV16 E2, E6 and E7 peptide pools. However, nearly fourfold higher T-cell reactivity against common antigens was found in the CIN women than in the healthy donors (p = 0.001). HPV16 E6 stimulation resulted in higher IL-17A secretion in the controls than in the CIN women (p = 0.035). Smoking and use of alcohol affected the T-cell response to common antigens but not to HPV peptides (p = 0.032 and 0.045, respectively).
  
  
  CONCLUSIONS
  While both the CIN women and controls exhibited an HPV16-specific CMI, IL-17A might be of importance in HPV induced pathology. The hyper-responsiveness of the CIN patients to common antigens needs further studies. Smoking and alcohol had no effect on HPV-specific CMI.
authors.affiliation: Medicity Research Laboratory and Department of Oral Pathology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland. aepaas@utu.fi.
authors.forename: Anna
authors.initials: A
authors.lastname: Paaso
authors.affiliation: Medicity Research Laboratory and Department of Oral Pathology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland. hakosk@utu.fi.
authors.forename: Hanna-Mari
authors.initials: HM
authors.lastname: Koskimaa
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands. M.J.P.Schoenmaekers-Welters@lumc.nl.
authors.forename: Marij Jp
authors.initials: MJ
authors.lastname: Welters
authors.affiliation: Department of Obstetrics and Gynaecology, Turku University Hospital, Turku, Finland. Seija.Grenman@tyks.fi.
authors.forename: Seija
authors.initials: S
authors.lastname: Grénman
authors.affiliation: Department of Clinical Research, Biohit Oyj, Helsinki, Finland. kari.syrjanen@biohit.fi.
authors.forename: Kari
authors.initials: K
authors.lastname: Syrjänen
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands. S.H.van_der_Burg@lumc.nl.
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
authors.affiliation: Medicity Research Laboratory and Department of Oral Pathology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland. stina.syrjanen@utu.fi.|Department of Oral Pathology, Institute of Dentistry, Faculty of Medicine, University of Turku, Lemminkäisenkatu 2, FI 20540, Turku, Finland. stina.syrjanen@utu.fi.
authors.forename: Stina
authors.initials: S
authors.lastname: Syrjänen
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D002584:Cervix Uteri / Q000378:metabolism / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry*; D005260:Female; D005387:Finland; D051858:Forkhead Transcription Factors / Q000378:metabolism; D052162:Human papillomavirus 16; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008137:Longitudinal Studies; D009061:Mouth Mucosa / Q000378:metabolism / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000737:chemistry*; D050725:Papillomavirus E7 Proteins / Q000737:chemistry*; D030361:Papillomavirus Infections / Q000276:immunology; D010455:Peptides / Q000737:chemistry; D012097:Repressor Proteins / Q000737:chemistry*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000821:virology
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C068651:E6 protein, Human papillomavirus type 16; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010455:Peptides; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16