Low level expression of human papillomavirus type 16 (HPV16) E6 in squamous epithelium does not elicit E6 specific B- or T-helper immunological responses, or influence the outcome of immunisation with E6 protein

Mice transgenic for E6/E7 oncogenes of Human Papillomavirus type 16 display life-long expression of E6 in lens and skin epithelium, and develop inflam matory skin disease late in life, which progresses to papillomata and squam ous carcinoma in some mice. We asked whether endogenous expression of E6 in duced a specific immunological outcome, i.e. immunity or tolerance, or whet her the mice remained immunologically naive to E6. We show that prior to th e onset of skin disease, E6 transgenic mice did not develop a spontaneous E 6-directed antibody response, nor did they display T-cell proliferative res ponses to dominant T-helper epitope peptides within E6. In contrast, old mi ce in which skin disease had arisen, developed antibodies to E6. We also sh ow that following immunisation with E6, specific antibody responses did not differ significantly among groups of EB-transgenic mice of different ages (and therefore of different durations and amounts of exposure to endogenous E6), and non-transgenic controls. Additionally, E6 immunisation-induced T- cell proliferative responses were similar in E6-transgenic and non-transgen ic mice. These data are consistent with the interpretation that unimmunised Eb-transgenic mice that have not developed inflammatory skin disease remai n immunologically naive to E6 at the B- and Th levels. There are implicatio ns for E6-mediated tumorigenesis in humans, and for the development of puta tive E6 therapeutic vaccines. (C) 2001 Elsevier Science B.V. All rights res erved.