title: CD4+ T cells against human papillomavirus-18 E7 in patients with high-grade cervical lesions associate with the absence of the virus in the cervix.
abstract: Cervical neoplastic lesions are associated with infection by high-risk human papilloma-viruses (HPV). The two genotypes most frequently found in the lesions are HPV-16 and HPV-18 with a prevalence of 50-60% and 15-18%, respectively. The E6 and E7 viral oncoproteins are involved in the transformation process and represent foreign antigens for the host. We previously reported that anti-HPV-18 E6 CD4(+) T cells are present in patients with high-grade HPV-18-expressing cervical lesions but also in 50% of the total consecutive patients tested, independently of the HPV type carried. These results indicated that HPV-18 E6 is immunogenic and suggested that all responsive patients, irrespective of the HPV expressed, had encountered HPV-18 and cleared the infection. Here, we investigated anti-HPV-18 E7 CD4(+) T-cell immunity in a cohort of 23 HPV-18 E6-responsive patients. We found that, although E7-specific CD4(+) T cells were present in all women, a robust T helper type (Th1)/Th2 type response against E7 was associated with HPV-18-negative status, suggesting that indeed these patients might have cleared the virus. In agreement with this hypothesis, we found strong anti-E7 CD4(+) T-cell immunity in 20% of 24 healthy donors without evidence of disease. In contrast, a robust Th1/Th2 type response against E6 but not E7 correlated with a lack of disease relapse and/or infection recurrence but did not discriminate between HPV-18-positive and HPV-18-negative patients. Collectively, our data suggest different roles for anti-HPV-18 E6 and E7 CD4(+) T cells in anti-viral and anti-tumour immunity.
authors.affiliation: Tumor Immunology Unit, Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Samantha
authors.initials: S
authors.lastname: Seresini
authors.forename: Massimo
authors.initials: M
authors.lastname: Origoni
authors.forename: Luigi
authors.initials: L
authors.lastname: Caputo
authors.forename: Flavia
authors.initials: F
authors.lastname: Lillo
authors.forename: Renato
authors.initials: R
authors.lastname: Longhi
authors.forename: Simone
authors.initials: S
authors.lastname: Vantini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Paganoni
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Protti
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000821:virology; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002584:Cervix Uteri / Q000821:virology*; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D005260:Female; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000276:immunology / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral