Ptaquiloside from bracken (Pteridium spp.) inhibits tumour-infiltrating CD8(+) T cells in HPV-16 transgenic mice

Abstract

Bracken is a fern with worldwide distribution. Exposure to bracken toxins such as ptaquiloside is hypothesized to increase the risk of papillomavirus-related cancers of the upper digestive tract. Ptaquiloside is thought to be an immunosupressor, thus allowing for the development of viral lesions. We have used a human papillomavirus type 16-transgenic (K14-HPV16) mouse model to study the effects of ptaquiloside on tumour-infiltrating CD8(+) T lymphocytes, which are critical players in anti-tumour immunity. HPV16(+/-) mice received ptaquiloside (0.5 mg/mouse/week) for 10 weeks. These were then euthanized at 30 weeks of age, along with age-matched untreated controls. Skin samples were enzymatically digested and CD8(+) T cells analysed for CD107a and CD44 surface expression. Ptaquilosideexposed HPV16(+/-) mice showed a significantly decreased percentage (P < 0.05) of CD8(+)CD107(+) and CD8(+)CD44 T cells when compared with untreated HPV16(+/)- animals. Histologically, 100% of ptaqui-losidetreated mice showed diffuse epidermal dysplasia, compared with 50% of the untreated mice. These findings suggest that ptaquiloside exerts an immunosuppressive role by decreasing CD8(+) T cell activation and degranulation in HPV-induced lesions. Given the key role of CD8(+) T lymphocytes against HPV-induced lesions, this effect is likely to contribute for viral persistence, tumour progression and increased aggressiveness in patients with HPV-related malignancies.