Autoreactive T cells induce necrosis and not BCL-2-regulated or death receptor-mediated apoptosis or RIPK3-dependent necroptosis of transplanted islets in a mouse model of type 1 diabetes
Yuxing Zhao, Nicholas A Scott, Stacey Fynch, Lorraine Elkerbout, W Wei-Lynn Wong, Kylie D Mason, Andreas Strasser, David C Huang, Thomas WH Kay, Helen E Thomas
DIABETOLOGIA | SPRINGER | Published : 2015
AIMS/HYPOTHESIS: Type 1 diabetes results from T cell-mediated destruction of pancreatic beta cells. The mechanisms of beta cell destruction in vivo, however, remain unclear. We aimed to test the relative roles of the main cell death pathways: apoptosis, necrosis and necroptosis, in beta cell death in the development of CD4(+) T cell-mediated autoimmune diabetes. METHODS: We altered expression levels of critical cell death proteins in mouse islets and tested their ability to survive CD4(+) T cell-mediated attack using an in vivo graft model. RESULTS: Loss of the B cell leukaemia/lymphoma 2 (BCL-2) homology domain 3-only proteins BIM, PUMA or BID did not protect beta cells from this death. Ove..View full abstract
This work was funded by a National Health and Medical Research Council of Australia (NHMRC) and Juvenile Diabetes Research Foundation (JDRF) joint special program grant in type 1 diabetes, program grants (HET, TWHK and AS) and fellowships from the NHMRC (HET and AS), a Leukemia and Lymphoma Society SCOR grant (AS) and a Postdoctoral Fellowship from the JDRF (YZ). The St Vincent's Institute and The Walter and Eliza Hall Institute receive support from the Operational Infrastructure Support Scheme of the Government of Victoria. This work was made possible through a Victorian State Government OIS grant and an Australian NHMRC IRIIS grant.