Coating of Human Pancreatic Islets with CD4+CD25highCD127- T Regulatory Cells - a Novel Immunosuppressive Approach
Piotr Witkowski*, Natalia Marek*, Adam Krzystyniak*, Ipek Ergenc*, Olivia Cochet*, Ryosuke Misawa*, Ling-Jia Wang*, Seda Kizilel*, Piotr Trzonkowski*, Jeffrey B. Matthews, J. Michael Millis*
University of Chicago, Chicago, IL
Rejection and immunosuppressant toxicity compromises the results of pancreatic islet transplantation. The aim of this study was to determine if T regulatory cells (Tregs) attached to islet cells modulate the immune reaction.
Human islets were coated with allogeneic ex-vivo expanded human Tregs using our previously developed protocol with biotinylated poly(ethylene glycol)-N-hydroxysuccinimide [biotin-PEG-NHS]. Viability and function of coated and native islets was compared using insulin-secretion dynamic perfusion assay.
Bonds between islets and Tregs were stable in culture. After 72h incubation with allogeneic T effector cells, Treg-coated islets revealed preserved function with higher insulin secretion compared to native, otherwise modified islets or when Tregs were added to the culture, but not attached to islets p< 0.05 (Figure). Additionally, ELISPOT assay revealed suppression of IFN-γ secretion when T effector cells were challenged with Treg-coated islets comparing to controls (99±7 vs 151±8 dots, respectively; p<0.009).
We have demonstrated for the first time the ability to bind immune regulatory cells to target cells and preserve viability of both cell types. Allogeneic Tregs attached to the islets showed their protective activity against immune attack. If these results are confirmed with in vivo studies, local delivery of immunosuppressive Tregs on the surface of pancreatic islets may be an alternative or improvement to the currently used maintenance immunosuppression after islet transplantation.
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