title: Anti-HPV16 E2 protein T-cell responses and viral control in women with usual vulvar intraepithelial neoplasia and their healthy partners.
abstract: T-cell responses (proliferation, intracellular cytokine synthesis and IFNγ ELISPOT) against human papillomavirus 16 (HPV16) E2 peptides were tested during 18 months in a longitudinal study in eight women presenting with HPV16-related usual vulvar intraepithelial neoplasia (VIN) and their healthy male partners. In six women, anti-E2 proliferative responses and cytokine production (single IFNγ and/or dual IFNγ/IL2 and/or single IL2) by CD4+ T lymphocytes became detectable after treating and healing of the usual VIN. In the women presenting with persistent lesions despite therapy, no proliferation was observed. Anti-E2 proliferative responses were also observed with dual IFNγ/IL2 production by CD4+ T-cells in six male partners who did not exhibit any genital HPV-related diseases. Ex vivo IFNγ ELISPOT showed numerous effector T-cells producing IFNγ after stimulation by a dominant E2 peptide in all men and women. Since the E2 protein is absent from the viral particles but is required for viral DNA replication, these results suggest a recent infection with replicative HPV16 in male partners. The presence of polyfunctional anti-E2 T-cell responses in the blood of asymptomatic men unambiguously establishes HPV infection even without detectable lesions. These results, despite the small size of the studied group, provide an argument in favor of prophylactic HPV vaccination of young men in order to prevent HPV16 infection and viral transmission from men to women.
authors.affiliation: Institut Cochin, Université Paris Descartes, CNRS, UMR 8104, Paris, France. simonjacobelli@gmail.com
authors.forename: Simon
authors.initials: S
authors.lastname: Jacobelli
authors.forename: Fedoua
authors.initials: F
authors.lastname: Sanaa
authors.forename: Micheline
authors.initials: M
authors.lastname: Moyal-Barracco
authors.forename: Monique
authors.initials: M
authors.lastname: Pelisse
authors.forename: Sophie
authors.initials: S
authors.lastname: Berville
authors.forename: Pascale
authors.initials: P
authors.lastname: Villefroy
authors.forename: Marie Odile
authors.initials: MO
authors.lastname: North
authors.forename: Suzanne
authors.initials: S
authors.lastname: Figueiredo
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Charmeteau
authors.forename: Thierry
authors.initials: T
authors.lastname: Clerici
authors.forename: Françoise
authors.initials: F
authors.lastname: Plantier
authors.forename: Françoise
authors.initials: F
authors.lastname: Arnold
authors.forename: Antoine
authors.initials: A
authors.lastname: Touzé
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupin
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
authors.forename: Jean-Gérard
authors.initials: JG
authors.lastname: Guillet
authors.forename: Rémi
authors.initials: R
authors.lastname: Cheynier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bourgault-Villada
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004279:DNA, Viral / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000473:pathology / Q000635:transmission; D014779:Virus Replication / Q000276:immunology; D014846:Vulvar Neoplasms / Q000276:immunology* / Q000473:pathology
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C508594:IL2 protein, human; D007376:Interleukin-2; D009856:Oncogene Proteins, Viral; D007371:Interferon-gamma