T cell-mediated and non-specific inflammatory mechanisms contribute to the skin pathology of HPV 16 E6E7 transgenic mice

Hilditch-Maguire, Paige A., Lieppe, Donna M., West, Donna M., Lambert, Paul F. and Frazer, Ian H. (1999) T cell-mediated and non-specific inflammatory mechanisms contribute to the skin pathology of HPV 16 E6E7 transgenic mice. Intervirology, 42 1: 43-50. doi:10.1159/000024959


Author Hilditch-Maguire, Paige A.
Lieppe, Donna M.
West, Donna M.
Lambert, Paul F.
Frazer, Ian H.
Title T cell-mediated and non-specific inflammatory mechanisms contribute to the skin pathology of HPV 16 E6E7 transgenic mice
Journal name Intervirology   Check publisher's open access policy
ISSN 0300-5526
Publication date 1999-01-01
Year available 1999
Sub-type Article (original research)
DOI 10.1159/000024959
Open Access Status Not yet assessed
Volume 42
Issue 1
Start page 43
End page 50
Total pages 8
Place of publication Basel
Publisher Karger
Language eng
Subject C1
320206 Tumor Immunology
730108 Cancer and related disorders
Abstract One of three lines of mice transgenic for the E6 and E7 genes of human papillomavirus type 16 (HPV16) expressed from an alpha A-crystallin promoter also expresses the transgene ectopically in the skin. This line, designated alpha ACE6E7#19, develops skin disease from 3 months of age, characterised by epidermal hyperplasia and eventual skin loss. Administration of complete Freund's adjuvant (CFA) to alpha ACE6E7#19 mice, but not to nontransgenic littermate controls, induced local epidermal hyperplasia which was histologically similar to the spontaneously arising skin pathology. Local application of 2,4-dinitrochlorobenzene (DNCB) to DNCB-sensitised aACE6E7#19 mice, but not DNCB-sensitised controls, also induced hyperplasia. Treatment with cyclosporin A (CsA) or systemic depletion of CD4+ cells significantly reduced the incidence of skin disease. These data suggest that local inflammation, and cytokines produced by T helper cells, contribute to the induction of hyperplastic skin disease in alpha ACE6E7#19 mice. Spontaneous skin disease with similar histological appearance, frequency, age of onset and severity in alpha ACE6E7#19 mice was observed in scid-/- aACE6E7#19 mice, despite immune paresis. Antigen-specific immune responses and T-cell cytokines a re therefore not necessary for the induction of skin disease. We propose that epidermal hyperplasia associated with HPV16 E6 and E7 expression in skin is accelerated by local secretion of pro-inflammatory cytokines, whose production can be enhanced by activated CD4+ T cells.
Keyword Virology
Hpv16
E7
Transgenic Mice
Alpha Ace6e7#19
Human Papillomavirus Type-16
Tumor-necrosis-factor
Cyclosporine-a
Human Keratinocytes
Protein
E7
Transformation
E7-oncoprotein
Cytokines
Epitopes
Q-Index Code C1
Grant ID R0-1 CA67366
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Mon, 13 Aug 2007, 21:13:26 EST