The immune responses of the Tasmanian devil (Sarcophilus harrisii) and the devil facial tumour disease

The Tasmanian devil (Sarcophilus harrisii) is a carnivorous marsupial endemic to the island-state of Tasmania, Australia and is currently under threat from a devastating disease named Devil Facial Tumour Disease (DFTD). This disease has been identified as a tumour, which starts in, or around, the mouth, face or neck and invariably causes the death of the affected animal within a few months after the first signs of disease. Recent cytogenetic and molecular research led to the proposal that the tumour is transmitted as an allograft after cellular inoculation (probably by biting) from an infected to a healthy animal. The transmissibility of this tumour by cell implantation raises many questions about the status of immune responses of Tasmanian devils and the MHC diversity of the species. Several aspects of the immune response of the Tasmanian devil were investigated to determine whether a lack of immune competence may account for the ability of DFTD to be established in recipient devils. Using histology and immunohistochemistry techniques, the immune tissues of healthy and diseased devils were described and provided evidence that the species has the necessary structural components for immune responses. However, DFTD tumours were also analysed using histology and immunohistochemistry and there appeared to be a lack of immune cell infiltration in the tumour grafts, suggesting that DFTD develops unrecognised by the immune system. To test the functional competency of cellular and humoral immune responses, a series of in vitro and in vivo assays was undertaken. Neutrophils and lymphocytes isolated from healthy and DFTD-affected Tasmanian devils utilised in in vitro neutrophil phagocytosis and lymphocyte mitogen stimulation showed competent cellular function. In vivo immunisation of Tasmanian devils with horse red blood cells resulted in prominent humoral immune responses. These results provided support for the concept that the species is not severely immunosuppressed and transmission of DFTD is not a consequence of an impaired immune response. Analyses of the allo-reactivity of the devil population were performed through in vitro mixed lymphocyte reactions and in vivo skin grafts between unrelated devils. Results from these experiments demonstrated that most devils had functional allo-recognition. Importantly, skin grafts between unrelated devils were immunologically rejected, indicating that spreading of DFTD is not simply due to a lack of MHC diversity in this species. To investigate whether immunity against DFTD could be induced, six Tasmanian devils were immunised with inactivated DFTD tumour cells. Most of these animals exhibited a very weak immune response against DFTD. Three of these devils were challenged with live DFTD tumour cells and succumbed to the disease. However, one devil had a more prominent antibody response against DFTD and was protected against a first challenge, suggesting that immunity was protective, but likely to be short-term. A survey for natural immune recognition of DFTD tumour cells in the devil population found one devil with antibodies against DFTD, and this animal was found a year later with no signs of the disease. This provided an insight that some individual devils might recognise and reject the tumour allograft.