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Mitogen activated Tasmanian devil blood mononuclear cells kill devil facial tumour disease cells


Brown, GK; Tovar, C; Cooray, AA; Kreiss, A; Darby, J; Murphy, JM; Corcoran, LM; Bettiol, SS; Lyons, AB; Woods, GM
2016-04-19
Immunology and Cell Biology
Journal Article
94
7
673-679
Devil Facial Tumour Disease (DFTD) is a transmissible cancer that has brought the host species, the Tasmanian devil, to the brink of extinction. The cancer cells avoid allogeneic immune recognition by down-regulating cell surface MHC I expression. This should prevent CD8+ T cell, but not NK cell, cytotoxicity. The reason why NK cells, normally reactive to MHC-negative cells, are not activated to kill DFTD cells has not been determined. The immune response of wild devils to DFTD, if it occurs, is uncharacterised. To investigate this, we tested twelve wild devils with DFTD, and found suggestive evidence of low levels of antibodies against DFTD cells in one devil. Eight of these devils were also analysed for cytotoxicity, however, none showed evidence for cytotoxicity against cultured DFTD cells. To establish whether mimicking activation of anti-tumour responses could induce cytotoxic activity against DFTD, Tasmanian devil peripheral blood mononuclear cells (PBMC) were treated with either the mitogen Concanavalin A, the toll-like receptor (TLR) agonist Poly I:C, or recombinant Tasmanian devil IL-2. All induced the PBMC cells to kill cultured DFTD cells, suggesting that activation does not occur after encounter with DFTD cells in vivo, but can be induced. The identification of agents that activate cytotoxicity against DFTD target cells is critical for developing strategies to protect against DFTD. Such agents could function as adjuvants to induce functional immune responses capable of targeting DFTD cells and tumours in vivo.Immunology and Cell Biology accepted article preview online, 19 April 2016. doi:10.1038/icb.2016.38.
NPG
Cell Signalling and Cell Death; Molecular Immunology
10.1038/icb.2016.38
27089941
Refer to article for additional funding acknowledgements
Refer to copyright notice on published article.

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Creation Date 2016-05-02 10:21:19 Last Modified 2018-07-05 08:59:41