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E7-specific cytotoxic T cell tolerance in HPV-transgenic mice
A Borchers1, J Braspenning, J Meijer
1Forschungsschwerpunkt für Angewandte Tumorvirologie, F0200, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Archives of Virology
|September 15, 1999
Summary
Human papillomavirus type 16 (HPV 16) E7 oncogene expression in mice induces immune tolerance at the cytotoxic T lymphocyte level. Vaccination elicits antibodies but not T cell responses, hindering anti-tumor immunity against HPV 16.
Area of Science:
- Oncology
- Immunology
- Virology
Background:
- High-risk human papillomavirus type 16 (HPV 16) is linked to cervical cancer.
- HPV 16 E6 and E7 oncoproteins are expressed in lesions but fail to elicit effective anti-tumor immunity.
- Keratinocytes are the primary cells targeted by HPV infection.
Purpose of the Study:
- To investigate the in vivo E7-specific immune response in HPV 16-associated cervical carcinogenesis.
- To analyze the immunological consequences of HPV 16 E6 and E7 transgene expression in mice.
Main Methods:
- Generation of transgenic mice expressing HPV 16 E6 and E7 oncogenes under the keratin 10 promoter.
- Analysis of immune responses, including antibody production and cytotoxic T lymphocyte (CTL) activity, following vaccination.
Main Results:
- Transgenic mice expressing E7 did not mount an endogenous immune response.
- Vaccination induced anti-E7 antibodies without autoimmune complications.
- E7-specific CTLs were notably absent after immunization.
Conclusions:
- Constitutive E7 expression in K10 HPV 16 E6/E7 transgenic mice induces specific immunological tolerance at the CTL level.
- This tolerance may explain the failure of the immune system to clear HPV 16-associated lesions.