Pa. Hilditch-maguire et al., T cell-mediated and non-specific inflammatory mechanisms contribute to theskin pathology of HPV 16 E6E7 transgenic mice, INTERVIROLO, 42(1), 1999, pp. 43-50
One of three lines of mice transgenic for the E6 and E7 genes of human papi
llomavirus type 16 (HPV16) expressed from an alpha A-crystallin promoter al
so expresses the transgene ectopically in the skin. This line, designated a
lpha ACE6E7#19, develops skin disease from 3 months of age, characterised b
y epidermal hyperplasia and eventual skin loss. Administration of complete
Freund's adjuvant (CFA) to alpha ACE6E7#19 mice, but not to nontransgenic l
ittermate controls, induced local epidermal hyperplasia which was histologi
cally similar to the spontaneously arising skin pathology. Local applicatio
n of 2,4-dinitrochlorobenzene (DNCB) to DNCB-sensitised aACE6E7#19 mice, bu
t not DNCB-sensitised controls, also induced hyperplasia. Treatment with cy
closporin 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 h
yperplastic 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 im
mune paresis. Antigen-specific immune responses and T-cell cytokines a re t
herefore not necessary for the induction of skin disease. We propose that e
pidermal hyperplasia associated with HPV16 E6 and E7 expression in skin is
accelerated by local secretion of pro-inflammatory cytokines, whose product
ion can be enhanced by activated CD4+ T cells.