title: Frequent display of human papillomavirus type 16 E6-specific memory t-Helper cells in the healthy population as witness of previous viral encounter.
abstract: Genital human papillomavirus (HPV) infection is common and the majority of infected individuals successfully deal with this virus. Clearance of HPV is presumably mediated by T cells but HPV-16-specific T-cell memory was usually detected in patients with progressive disease and not in healthy subjects, suggesting that HPV-immunity comes too late. We now show the presence of HPV-16 E6-specific memory T-helper (Th) responses in a major fraction (12 of 20) of healthy individuals by application of the IFN-gamma-ELISPOT assay. Although nearly all E6-peptides were recognized, the majority of the responders targeted peptide sequences of the COOH-terminal half (E6(81-158)) of HPV-16 E6. In a direct comparison, the presence of HPV-16 E6-specific T cells coincided with HPV-16 E2-specific T-cell reactivity in healthy individuals, whereas hardly any HPV-16 E7-specific Th immunity was found. This indicates that the induction of T-cell reactivity against HPV-16 E7 is suboptimal during infection when compared with that against HPV-16 E2 and HPV-16 E6. In conclusion, the presence of HPV-16 E6-specific Th memory in the healthy population demonstrates that HPV infection leads to T-cell immunity against immediate early proteins expressed during infection. Because this HPV-16 E6-specific T-cell immunity was frequently detected in healthy subjects, our data suggest that the observed IFN-gamma-producing proliferating T cells circulating in the peripheral blood play a role in protection against persistent HPV infection and associated development of malignancies.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Marij J P
authors.initials: MJ
authors.lastname: Welters
authors.forename: Annemieke
authors.initials: A
authors.lastname: de Jong
authors.forename: Susan J F
authors.initials: SJ
authors.lastname: van den Eeden
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: van der Hulst
authors.forename: Kitty M C
authors.initials: KM
authors.lastname: Kwappenberg
authors.forename: Sabrin
authors.initials: S
authors.lastname: Hassane
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Jan Wouter
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: Gemma
authors.initials: G
authors.lastname: Kenter
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Rienk
authors.initials: R
authors.lastname: Offringa
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
mesh_terms: D000328:Adult; D000368:Aged; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D012097:Repressor Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D014412:Tumor Virus Infections / Q000276:immunology* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000821:virology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D018984:Epitopes, T-Lymphocyte; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma