The Immune Response of the Tasmanian Devil (Sarcophilus harrisii) and Devil Facial Tumour Disease

Abstract

One of the most remarkable aspects of Devil Facial Tumour Disease (DFTD) is its infectious nature, and for successful transmission it must avoid detection by the devil's immune system. For this to occur, the devil either is severely immunosuppressed or factors produced by the tumor contribute to its avoidance of immune detection. An analysis of the devil's immune system revealed the presence of normal-looking lymphoid organs and lymphoid cells. At a functional level the lymphocytes proliferated in response to mitogen stimulation. Subcutaneous injection of a cellular antigen produced a strong antibody response, providing compelling evidence that the devil has a competent immune system. Tumor cell analysis demonstrated that the tumor expresses the genes of the major histocompatibility complex; however, there was a limited diversity. Therefore, the most likely explanation for devil-to-devil transmission of DFTD is that the tumor is not recognized by the devil as ''non-self'' because of the limited genetic diversity. With its consistent morphology and relatively stable genome, this tumor would provide a reasonable target for a vaccine approach, provided the immune system can be coaxed into recognizing the tumor as ''non-self.''

Disease and the dynamics of extinction

“…Developing vaccines for pathogens that affect only wildlife is likely to be prohibitively expensive in most cases. There has been research into developing a vaccine for DFTD [114,115], but it has yet to result in an effective vaccine.…”

Clonally transmissible cancers in dogs and Tasmanian devils

“…Siddle et al (2007a) confirmed that MHC class I and II genes are expressed in DFTD tumors at the mRNA level, although further studies are required to determine whether MHC genes in DFTD are correctly translated, trafficked and displayed (Table 1). The lack of diversity at MHC loci, coupled with weak responses of east coast devils to allogeneic mixed lymphocyte culture, has led to the suggestion that this population may be functionally identical at MHC loci, thus permitting the spread of DFTD as an allograft ( Figure 2; Woods et al, 2007;Siddle et al, 2007a;Kreiss et al, 2008). However, as other marsupials have been reported to have weak responses to mixed lymphocyte culture, and antigens other than MHC also contribute to immunosurveillance, this model is yet to be confirmed (Montali et al, 1998;Stone et al, 1998;Janeway et al, 2001).…”

“…Devil neutrophils are competent at bacterial phagocytosis and degradation, and lymphocyte proliferation can be stimulated by a variety of mitogens (Woods et al, 2007;Siddle et al, 2007a;Kreiss et al, 2008). Lymphocyte proliferation responses varied greatly between individual Tasmanian devils, and lymphocytes from animals with DFTD responded similarly to those of healthy devils (Woods et al, 2007;Kreiss et al, 2008).…”

“…These experiments confirm that DFTD does not induce general suppression of lymphocyte stimulation or proliferation. Furthermore, devils are able to mount humoral responses to exogenous antigens and retain immunological memory (Woods et al, 2007;Kreiss et al, 2009). The discovery of antibodies recognizing DFTD in at least one devil (Obendorf and McGlashan, 2008), together with the observation of possible plasmacytosis in DFTD-affected devils (Woods et al, 2007), raises the possibility that at least some devils may mount humoral responses to DFTD.…”

Catching Cancer

“…MHC-incompatible tumor cells transplanted from a parental strain onto an F1 hybrid showed the recipient's immune system responded against tumor cells that had not lost their MHC molecules [27]. Interestingly, Tasmanian devils maintain effective immune system and yet do not display an immune response to DFTD [28,29]. However, nude (immunodeficient) mice injected subcutaneously with DFTD cells rapidly developed tumors, indicating a lack of immunoresponsiveness enabled tumor progression [30].…”