On-target and direct modulation of alloreactive T cells by a nanoparticle carrying MHC alloantigen, regulatory molecules and CD47 in a murine model of alloskin transplantation.

On-target and direct modulation of alloreactive T cells by a nanoparticle carrying MHC alloantigen, regulatory molecules and CD47 in a murine model of alloskin transplantation. Drug Deliv. 2018 Nov;25(1):703-715 Authors: Shahzad KA, Wan X, Zhang L, Pei W, Zhang A, Younis M, Wang W, Shen C Abstract Biomimetic nanoparticles have been reported as immune modulators in autoimmune diseases and allograft rejections by numerous researchers. However, most of the therapeutics carrying antigens, toxins or cytokines underlay the mechanism of antigen presentation by cellular uptake of NPs through pinocytosis and phagocytosis. Few researches focus on the direct and antigen-specific modulation on T cells by NPs and combined use of multiple regulatory molecules. Here, polylactic-co-glycolic acid nanoparticles (PLGA-NPs) were fabricated as scaffold to cocoupling H-2Kb-Ig dimer, anti-Fas mAb, PD-L1-Fc, TGF-β and CD47-Fc for the generation of alloantigen-presenting and tolerance-inducing NPs, termed killer NPs and followed by i.v. injection into a single MHC-mismatched murine model of alloskin transplantation. Three infusions prolonged alloskin graft survival for 45 days; depleted most of H-2Kb alloreactive CD8+ T cells in peripheral blood, spleen and local graft, in an antigen-specific manner. The killer NPs circulated throughout vasculature into various organs and local allograft, with a retention time up to 30 h. They made contacts with CD8+ T cell...
Source: Drug Delivery - Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research