• Annals of surgery · Sep 2011

    Coating human pancreatic islets with CD4(+)CD25(high)CD127(-) regulatory T cells as a novel approach for the local immunoprotection.

    • Natalia Marek, Adam Krzystyniak, Ipek Ergenc, Olivia Cochet, Ryosuke Misawa, Ling-Jia Wang, Karolina Gołąb, Xiaojun Wang, German Kilimnik, Manami Hara, Seda Kizilel, Piotr Trzonkowski, J Michael Millis, and Piotr Witkowski.
    • Department of Surgery, Section of Transplantation, University of Chicago, IL 60637, USA.
    • Ann. Surg. 2011 Sep 1; 254 (3): 512-8; discussion 518-9.

    ObjectivesTo develop a novel approach for local immunoprotection using CD4(+)CD25(high)CD127(-) T regulatory cells (Tregs) attached to the surface of the islets before transplantation.BackgroundTregs expanded ex vivo can control allo and autoreactivity, therefore, Treg-based therapy may offer more effective protection for transplanted islets from immunologic attack than currently used immunosuppression. Local application of Tregs can make such therapy more clinically feasible and efficient.MethodsHuman islets were isolated and coated with allogeneic ex vivo expanded Tregs using biotin-poly(ethylene glycol)-N-hydroxysuccinimide ester (biotin-PEG-NHS) and streptavidin as binding molecules.ResultsCoating pancreatic islets with Tregs did not affect islet viability (>90% fluorescein diacetate/propidium iodide) or the insulin secretion profile in dynamic islet perifusion assays. After in vitro incubation with allogeneic T effector cells, Treg-coated islets revealed preserved function with higher insulin secretion compared with controls-native islets, coated islets with T effector cells or when Tregs were added to the culture, but not attached to islets (P < 0.05). In addition, the Enzyme-linked immunosorbent spot (ELISPOT) assay revealed suppression of interferon (IFN)-γ secretion, when T effector cells were challenged with Treg-coated islets comparing to controls (99 ± 7 vs 151 ± 8 dots, respectively; P < 0.01).ConclusionsWe demonstrated, for the first time, the ability to bind immune regulatory cells to target cells with preservation of their viability and function and protective activity against immune attack. If successfully tested in an animal model, local delivery of immunoprotective Tregs on the surface of transplanted pancreatic islets may be an alternative or improvement to the currently used immunosuppression.

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