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Human T cell responses to HPV 16 E2 generated with monocyte-derived dendritic cells.
E J Davidson1, M D Brown, D J Burt
1CRC Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom.
International Journal of Cancer
|December 18, 2001
Summary
Human papillomavirus (HPV) E2 protein-pulsed dendritic cells stimulate T cells, generating HPV E2-specific cytotoxic T lymphocytes (CTLs). These CTLs can target and lyse HPV-infected cells, offering potential for cervical cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Persistent human papillomavirus (HPV) type 16 infection is linked to cervical cancer development.
- The HPV E2 protein is crucial for early viral replication, making it a potential target for immune interventions.
- Developing vaccines or therapies against premalignant HPV lesions requires identifying effective immune targets.
Purpose of the Study:
- To investigate if dendritic cells (DCs) pulsed with HPV 16 E2 C-terminus protein can stimulate T cells.
- To assess the ability of stimulated T cells to recognize and lyse HPV E2-expressing target cells.
- To explore the potential of HPV E2 as an immunotherapeutic target for HPV-associated diseases.
Main Methods:
- Dendritic cells (DCs) were prepared from monocytes and pulsed with bacterially produced HPV 16 E2 C-terminus protein.
- Autologous T cells were stimulated with E2-pulsed DCs.
- Gamma-interferon release was measured by ELISPOT, and cytotoxic activity was assessed by (51)chromium release assays using autologous Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs) infected with a recombinant vaccinia virus encoding HPV 16 E2.
Main Results:
- DC pulsed with E2 C-terminus protein successfully induced gamma-interferon-releasing T cells.
- CD8+ cytotoxic T lymphocytes (CTLs) demonstrated E2-specific lysis of autologous LCLs infected with vaccinia-E2.
- CTLs did not lyse untreated LCLs or LCLs infected with wild-type vaccinia, confirming E2 specificity.
Conclusions:
- Dendritic cell-based immunotherapy can induce HPV E2-specific T-cell responses.
- CD8+ CTLs generated against HPV E2 exhibit specific cytotoxic activity against HPV-infected cells.
- These findings support the development of immunotherapeutic strategies targeting HPV E2 for cervical intraepithelial neoplasia and other HPV-associated diseases.