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dc.contributor.authorDe Gruijl, T D
dc.contributor.authorBontkes, H J
dc.contributor.authorWalboomers, J M
dc.contributor.authorStukart, M J
dc.contributor.authorDoekhie, F S
dc.contributor.authorRemmink, A J
dc.contributor.authorHelmerhorst, T J
dc.contributor.authorVerheijen, R H
dc.contributor.authorDuggan-Keen, Margaret F
dc.contributor.authorStern, Peter L
dc.contributor.authorMeijer, C J
dc.contributor.authorScheper, R J
dc.date.accessioned2010-02-25T11:30:21Z
dc.date.available2010-02-25T11:30:21Z
dc.date.issued1998-04-15
dc.identifier.citationDifferential T helper cell responses to human papillomavirus type 16 E7 related to viral clearance or persistence in patients with cervical neoplasia: a longitudinal study. 1998, 58 (8):1700-6 Cancer Res.en
dc.identifier.issn0008-5472
dc.identifier.pmid9563486
dc.identifier.urihttp://hdl.handle.net/10541/93023
dc.description.abstractT-cell-mediated immune responses against oncogenic human papillomaviruses (HPVs) are believed to play a role in the prevention of cervical carcinogenesis. The in vitro production of interleukin 2 by CD4+ T helper (Th) cells in response to overlapping 20-mer peptides covering the HPV-16 E7 oncoprotein sequence was determined in 72 women with cytological evidence of premalignant cervical intraepithelial neoplasia (CIN) who participated in a nonintervention follow-up (FU) study. In addition, 15 HPV-16 + cervical carcinoma patients were tested. Positive Th cell reactivity was restricted to patients infected by HPV-16 and related types and showed a strong association with viral persistence and disease progression, as evidenced by the high frequency of positive responders among women with persistent HPV-16 infections who ended FU with high-grade CIN III lesions [14 of 15 (93%)]. Women with cervical carcinoma showed responses at a significantly reduced rate [7 of 15 (47%); P = 0.014]. Over the FU period (10-34 months), the level of E7-induced interleukin 2 production from the lymphocytes of CIN patients who had cleared HPV-16 infection showed an inverse correlation with time relative to the last positive HPV DNA test, with 8 of 13 of these patients showing positive responses after clearance. By contrast, among women with persistent HPV-16 infections and developing CIN III lesions (n = 8), there was a rise in Th cell activity over the course of FU. The majority of women responded to an immunogenic region in the carboxyl terminus of the E7 protein (amino acids 67-98). The observed HPV-16 E7-specific Th cell responses may develop as a consequence of increased antigen availability resulting either from clearance or from progression of cervical lesions.
dc.language.isoenen
dc.subjectUterine Cervical Canceren
dc.subject.meshAdult
dc.subject.meshCarcinoma
dc.subject.meshCells, Cultured
dc.subject.meshCervical Intraepithelial Neoplasia
dc.subject.meshFemale
dc.subject.meshHLA-DQ Antigens
dc.subject.meshHLA-DR Antigens
dc.subject.meshHumans
dc.subject.meshInterleukin-2
dc.subject.meshLeukocytes, Mononuclear
dc.subject.meshLongitudinal Studies
dc.subject.meshMiddle Aged
dc.subject.meshOncogene Proteins, Viral
dc.subject.meshProspective Studies
dc.subject.meshT-Lymphocytes, Helper-Inducer
dc.subject.meshUterine Cervical Neoplasms
dc.titleDifferential T helper cell responses to human papillomavirus type 16 E7 related to viral clearance or persistence in patients with cervical neoplasia: a longitudinal study.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology, Free University Hospital, Amsterdam, The Netherlands.en
dc.identifier.journalCancer Researchen
html.description.abstractT-cell-mediated immune responses against oncogenic human papillomaviruses (HPVs) are believed to play a role in the prevention of cervical carcinogenesis. The in vitro production of interleukin 2 by CD4+ T helper (Th) cells in response to overlapping 20-mer peptides covering the HPV-16 E7 oncoprotein sequence was determined in 72 women with cytological evidence of premalignant cervical intraepithelial neoplasia (CIN) who participated in a nonintervention follow-up (FU) study. In addition, 15 HPV-16 + cervical carcinoma patients were tested. Positive Th cell reactivity was restricted to patients infected by HPV-16 and related types and showed a strong association with viral persistence and disease progression, as evidenced by the high frequency of positive responders among women with persistent HPV-16 infections who ended FU with high-grade CIN III lesions [14 of 15 (93%)]. Women with cervical carcinoma showed responses at a significantly reduced rate [7 of 15 (47%); P = 0.014]. Over the FU period (10-34 months), the level of E7-induced interleukin 2 production from the lymphocytes of CIN patients who had cleared HPV-16 infection showed an inverse correlation with time relative to the last positive HPV DNA test, with 8 of 13 of these patients showing positive responses after clearance. By contrast, among women with persistent HPV-16 infections and developing CIN III lesions (n = 8), there was a rise in Th cell activity over the course of FU. The majority of women responded to an immunogenic region in the carboxyl terminus of the E7 protein (amino acids 67-98). The observed HPV-16 E7-specific Th cell responses may develop as a consequence of increased antigen availability resulting either from clearance or from progression of cervical lesions.


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