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Cancer Res ; 63(3): 636-41, 2003 Feb 01.
Article in English | MEDLINE | ID: mdl-12566307

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.


Subject(s)
Oncogene Proteins, Viral/immunology , Papillomaviridae/immunology , Papillomavirus Infections/immunology , Repressor Proteins , T-Lymphocytes, Helper-Inducer/immunology , Tumor Virus Infections/immunology , Adult , Aged , Epitopes, T-Lymphocyte/immunology , Female , Humans , Immunologic Memory/immunology , Interferon-gamma/immunology , Interferon-gamma/metabolism , Lymphocyte Activation/immunology , Male , Middle Aged , Papillomavirus E7 Proteins , Papillomavirus Infections/virology , T-Lymphocytes, Helper-Inducer/metabolism , Tumor Virus Infections/virology , Uterine Cervical Neoplasms/immunology , Uterine Cervical Neoplasms/virology
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