Date/Time
Date(s) - Wed 21 June
12:30
Location
Maclaurin Lecture Theatre (MCLT) 103, VUW
Prof. Frazer is one of Australian’s National Treasures, his groundbreaking and pioneering research on virus-like particles and vaccine-induced immunity to Human Papilloma Virus (HPV) led to the development of the first HPV vaccine against cervical cancer. Prof. Frazer’s current work includes the investigation of immunoregulation during chronic viral infections.
Abstract
Persistent infection with high-risk Human Papilloma Viruses is associated with cervical intraepithelial neoplasia (CIN). Understanding the immune response invoked in precancer associated with persisting HPV will aid the development of a therapeutic vaccine against chronic HPV infection. Mice transgenic for HPV16 viral oncoprotein E7, with expression directed to the epidermis (K14E7 mice) display epidermal hyperplasia and suppressed immune responses to E7 with increased skin lymphocytic infiltration. However, E7 transgenic mice with disrupted E7-Rb interaction due to a mutated Rb protein (K14.E7xRb9) present with normoplastic skin and no discernible immune dysfunction. We have evaluated RNA expression profile of K14E7 transgenic skin and the function of T cells derived from the transgenic skin. The RNA expression profile of K14.E7 skin significantly correlated with that associated with CD4+ and CD8+ T cell exhaustion. Additionally, increased expression of message and protein for immune check-point molecules was observed. T cells activated in vitro and transferred to K14E7 mice acquired PD-1 and CTLA4 expression in skin. In contrast to T cells from K14.E7 transgenic animals, T cells from skin of K14.E7 transgenic animals lacking epithelial proliferation and exhibited reduced immune check-point molecule expression. These findings suggest, in a model of persistent HPV infection, that epithelial hyperplasia is associated with T cell immunoregulation, possibly induced by local expression of immune checkpoint molecules.