Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes
Kriti Joshi, Colleen Elso, Ali Motazedian, Tanya Labonne, Jacqueline V Schiesser, Fergus Cameron, Stuart I Mannering, Andrew G Elefanty, Edouard G Stanley
Diabetologia | SPRINGER | Published : 2019
AIMS/HYPOTHESIS: Type 1 diabetes is an autoimmune disorder characterised by loss of insulin-producing beta cells of the pancreas. Progress in understanding the cellular and molecular mechanisms underlying the human disease has been hampered by a dearth of appropriate human experimental models. We previously reported the characterisation of islet-infiltrating CD4+ T cells from a deceased organ donor who had type 1 diabetes. METHODS: Induced pluripotent stem cell (iPSC) lines derived from the above donor were differentiated into CD14+ macrophages and tested for their capacity to present antigen to T cell receptors (TCRs) derived from islet-infiltrating CD4+ T cells from the same donor. RESULTS..View full abstract
Awarded by National Health and Medical Research Council (Australia)
Awarded by JDRF
Awarded by Diabetes Australia
This study was supported by grants from the National Health and Medical Research Council (Australia; GNT1068866, GNT1079004, GNT1117596, GNT1129861, GNT1138717), the JDRF (3-SRA-201860-3-M-B) and Diabetes Australia (Y19G-STAE). KJ was supported by the Aitken Diabetes Fellowship of the Royal Children's Hospital Melbourne and the Murdoch Children's Research Institute. EGS and AGE are Research Fellows of the National Health and Medical Research Council (Australia).