Human T-cell responses to HPV 16 E2 generated with monocyte-derived dendritic cells

Davidson, Emma J.; Brown, Michael D.; Burt, Deborah J.; Parish, Joanna L.; Gaston, Kevin; Kitchener, Henry C.; Stacey, Simon N.; Stern, Peter L.

Abstract

Persistent infection with human papillomavirus (HPV) type 16 has been implicated in the etiology of cervical cancer. The E2 protein is required early in viral infection and therefore may serve as a useful immune target for a vaccine aimed at prevention or therapy of premalignant lesions. Dendritic cells (DC) prepared from monocytes and pulsed with bacterially produced HPV 16 E2 C‐terminus protein were used to stimulate autologous T cells over several rounds of stimulation. T cells were tested for γ‐interferon release by ELISPOT and for cytotoxic activity by 51chromium release assays. To generate E2‐expressing target cells for cytotoxicity assays, we constructed a recombinant vaccinia virus encoding HPV 16 E2, which was used to infect autologous Epstein‐Barr virus‐transformed lymphoblastoid cell lines (LCL). The results show that DC pulsed with E2 C‐terminus protein induce γ‐interferon‐releasing T cells as demonstrated by ELISPOT. Furthermore, we demonstrate E2‐specific lysis of vaccinia‐E2 infected autologous LCL by CD8+ cytotoxic T lymphocytes (CTL). E2‐specific CTL did not lyse untreated autologous LCL or LCL infected with wild‐type vaccinia and showed low levels of cytotoxicity against natural killer cell‐sensitive K562 cells. In addition, T cells stimulated with DC in the absence of E2 failed to demonstrate lysis of vaccinia‐E2‐labeled targets. Phenotypically, CTL populations were CD3+/CD8+. These results will facilitate the study of naturally occurring T‐cell responses to HPV E2 in patients with cervical intraepithelial neoplasia and the development of immunotherapeutic strategies designed to treat this and other HPV‐associated diseases. © 2001 Wiley‐Liss, Inc.

Citation

Davidson, E. J., Brown, M. D., Burt, D. J., Parish, J. L., Gaston, K., Kitchener, H. C., Stacey, S. N., & Stern, P. L. (2001). Human T-cell responses to HPV 16 E2 generated with monocyte-derived dendritic cells. International Journal of Cancer, 94(6), 807-812. https://doi.org/10.1002/ijc.1558

• Journal Article Type: Article
• Acceptance Date: Jul 4, 2001
• Publication Date: Dec 15, 2001
• Deposit Date: Nov 6, 2018
• Journal: International Journal of Cancer
• Print ISSN: 0020-7136
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 94
• Issue: 6
• Pages: 807-812
• DOI: https://doi.org/10.1002/ijc.1558
• Public URL: https://nottingham-repository.worktribe.com/output/1037818
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.1558