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

Samantha Seresini, Massimo Origoni, Luigi Caputo, Flavia Lillo, Renato Longhi, Simone Vantini, Anna Maria Paganoni, Maria Pia Protti

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)89-98
Number of pages10
JournalImmunology
Volume131
Issue number1
DOIs
Publication statusPublished - Sep 2010

Keywords

  • CD4 T cells
  • E6 and E7 proteins
  • high-grade cervical lesions
  • human papillomavirus type 18

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this