Anti-HPV16 E2 protein T-cell responses and viral control in women with usual vulvar intraepithelial neoplasia and their healthy partners

• Published in: PloS one Vol. 7; no. 5; p. e36651
• Main Authors: Jacobelli, Simon, Sanaa, Fedoua, Moyal-Barracco, Micheline, Pelisse, Monique, Berville, Sophie, Villefroy, Pascale, North, Marie Odile, Figueiredo, Suzanne, Charmeteau, Bénédicte, Clerici, Thierry, Plantier, Françoise, Arnold, Françoise, Touzé, Antoine, Dupin, Nicolas, Avril, Marie-Françoise, Guillet, Jean-Gérard, Cheynier, Rémi, Bourgault-Villada, Isabelle
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09-05-2012; Public Library of Science (PLoS)
• Subjects: Adult; Biology; Cancer; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; Cellular biology; Correlation analysis; Cytokines; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA replication; DNA, Viral - immunology; DNA-Binding Proteins - immunology; Drug therapy; E2 protein; Effector cells; Enzyme-linked immunosorbent assay; Enzyme-Linked Immunospot Assay; Female; Gene expression; Genomes; HIV; Human health and pathology; Human immunodeficiency virus; Human papillomavirus; Human papillomavirus 16 - physiology; Humans; Immunity, Cellular; Infections; Interferon-gamma - immunology; Interleukin 2; Interleukin-2 - immunology; Lesions; Life Sciences; Lymphocytes; Lymphocytes T; Male; Medicine; Men; Middle Aged; Oncogene Proteins, Viral - immunology; Papillomavirus infections; Papillomavirus Infections - immunology; Papillomavirus Infections - pathology; Papillomavirus Infections - transmission; Peptides; Polymerase chain reaction; Proteins; T cell receptors; T cells; Vaccination; Viral infections; Virus Replication - immunology; Vulvar Neoplasms - immunology; Vulvar Neoplasms - pathology; Vulvar Neoplasms - veterinary; Women; Womens health; γ-Interferon; France; E6; E7; HUMAN-PAPILLOMAVIRUS TYPE-16; FUNCTIONAL SIGNATURES; CD4+T-CELL IMMUNITY; MALE SEXUAL PARTNERS; HPV16 E2; CERVICAL-CANCER; INFECTION; LESIONS
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0036651

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.