Engineering an “infectious” Treg biomimetic through chemoselective tethering of TGF-β1 to PEG brush surfaces

Abstract Modulation of immunological responses to allografts following transplantation is of pivotal importance to improving graft outcome and duration. Of the many approaches, harnessing the dominant tolerance induced by regulatory T cells (T reg ) holds tremendous promise. Recent studies have highlighted the unique potency of cell surface-bound TGF-β1 on T reg for promoting infectious tolerance, i.e. to confer suppressive capacity from one cell to another. To mimic this characteristic, TGF-β1 was chemoselectively tethered to inert and viable polymer grafting platforms using Staudinger ligation. We report the synthesis and functional characterization of these engineered TGF-β1 surfaces. Inert beads tethered with TGF-β1 were capable of efficiently converting naive CD4 + CD62L hi T cells to functional T reg . Concordantly, translation of conjugation scheme from inert surfaces to viable cells also led to efficient generation of functional T reg . Further, the capacity of these platforms to generate antigen-specific T reg was demonstrated. These findings illustrate the unique faculty of tethered TGF-β1 biomaterial platforms to function as an “infectious” T reg and provide a compelling approach for generating tolerogenic microenvironments for allograft transplantation.