Hydrogen-bonded multilayers of tannic acid as mediators of T-cell immunity.

Abstract

Type 1 diabetes is an autoimmune-mediated disease resulting in the destruction of insulin-secreting pancreatic β-cells. Transplantation of insulin-producing islets is a viable treatment to restore euglycemia in Type 1 diabetics; however, the clinical application remains limited due to the use of toxic immunosuppressive therapies to prevent immune-mediated rejection. A nanothin polymer material with dual antioxidant and immunosuppressive properties capable of modulating both innate and adaptive immune responses crucial for transplantation outcome is presented. Through the use of hollow microparticles (capsules) composed of hydrogen-bonded multilayers of natural polyphenol (tannic acid) with poly(N-vinylpyrrolidone) (TA/PVPON) and with poly(N-vinylcaprolactam) (TA/PVCL), proinflammatory reactive oxygen and nitrogen species are efficiently dissipated and the production of interferon (IFN)-γ and tumor necrosis factor (TNF)-α proinflammatory cytokines is attenuated by cognate antigen-stimulated autoreactive CD4+ T cells. These results provide evidence that TA-containing capsules are efficacious in immunomodulation and may provide physical transplant protection and prevent diabetogenic autoreactive T-cell responses. Future studies will determine if xeno- and allotransplantation with (TA/PVPON)- or (TA/PVCL)-coated pancreatic islets will decrease the risk of graft rejection due to attenuation of oxidative stress and IFN-γ, and restore euglycemia in Type 1 diabetics.