TY - JOUR
T1 - Frequent display of human papillomavirus type 16 E6-specific memory t-Helper cells in the healthy population as witness of previous viral encounter
AU - Welters, Marij J P
AU - de Jong, Annemieke
AU - van den Eeden, Susan J F
AU - van der Hulst, Jeanette M
AU - Kwappenberg, Kitty M C
AU - Hassane, Sabrin
AU - Franken, Kees L M C
AU - Drijfhout, Jan Wouter
AU - Fleuren, Gert Jan
AU - Kenter, Gemma
AU - Melief, Cornelis J M
AU - Offringa, Rienk
AU - van der Burg, Sjoerd H
N1 - https://aacrjournals.org/cancerres/article/63/3/636/510959/Frequent-Display-of-Human-Papillomavirus-Type-16
PY - 2003/2/1
Y1 - 2003/2/1
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Epitopes, T-Lymphocyte/immunology
KW - Female
KW - Humans
KW - Immunologic Memory/immunology
KW - Interferon-gamma/immunology
KW - Lymphocyte Activation/immunology
KW - Male
KW - Middle Aged
KW - Oncogene Proteins, Viral/immunology
KW - Papillomaviridae/immunology
KW - Papillomavirus E7 Proteins
KW - Papillomavirus Infections/immunology
KW - Repressor Proteins
KW - T-Lymphocytes, Helper-Inducer/immunology
KW - Tumor Virus Infections/immunology
KW - Uterine Cervical Neoplasms/immunology
M3 - Article
C2 - 12566307
SN - 0008-5472
VL - 63
SP - 636
EP - 641
JO - Cancer Research
JF - Cancer Research
IS - 3
ER -