natural killer cell mediated cytotoxic responses in the tasmanian devil自然杀手细胞介导的细胞毒性反应的袋獾.pdfVIP

Natural Killer Cell Mediated Cytotoxic Responses in the Tasmanian Devil 1 1 2 1 Gabriella K. Brown , Alexandre Kreiss , A. Bruce Lyons , Gregory M. Woods * 1 Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia, 2 School of Medicine, University of Tasmania, Hobart, Tasmania, Australia Abstract The Tasmanian devil (Sarcophilus harrisii), the world’s largest marsupial carnivore, is under threat of extinction following the emergence of an infectious cancer. Devil facial tumour disease (DFTD) is spread between Tasmanian devils during biting. The disease is consistently fatal and devils succumb without developing a protective immune response. The aim of this study was to determine if Tasmanian devils were capable of forming cytotoxic antitumour responses and develop antibodies against DFTD cells and foreign tumour cells. The two Tasmanian devils immunised with irradiated DFTD cells did not form cytotoxic or humoral responses against DFTD cells, even after multiple immunisations. However, following immunisation with xenogenic K562 cells, devils did produce cytotoxic responses and antibodies against this foreign tumour cell line. The cytotoxicity appeared to occur through the activity of natural killer (NK) cells in an antibody dependent manner. Classical NK cell responses, such as innate killing of DFTD and foreign cancer cells, were not observed. Cells with an NK-like phenotype comprised approximately 4 percent of peripheral blood mononuclear cells. The results of this study suggest that Tasmanian devils have NK cells with functional cytotoxic pathways. Although devil NK cells do not directly recognise DFTD cancer cells, the development of ant