Differential T helper cell responses to human papillomavirus type 16 E7 related to viral clearance or persistence in patients with cervical neoplasia: a longitudinal study
| Autor: | T D, de Gruijl, H J, Bontkes, J M, Walboomers, M J, Stukart, F S, Doekhie, A J, Remmink, T J, Helmerhorst, R H, Verheijen, M F, Duggan-Keen, P L, Stern, C J, Meijer, R J, Scheper |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Adult
Papillomavirus E7 Proteins Carcinoma Uterine Cervical Neoplasms HLA-DR Antigens Oncogene Proteins Viral T-Lymphocytes Helper-Inducer Middle Aged Uterine Cervical Dysplasia HLA-DQ Antigens Leukocytes Mononuclear Humans Interleukin-2 Female Longitudinal Studies Prospective Studies Cells Cultured |
| Zdroj: | Cancer research. 58(8) |
| ISSN: | 0008-5472 |
| Popis: | T-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|