Inhibition of islet allograft rejection by Qa-1/PD-L1 artificial liposome

Abstract

Objective To explore the effects of Qa-1 and PD-L1 loaded artificial liposomal treatment in allograft rejection and its outcomes. Methods The extracellular domains of Qa-1 and PD-L1 were loaded on liposome surface by streptavidin-biotin system. Mixed lymphocyte reaction (MLR) was performed for measuring Qa-1/PD-L1 liposome biological function. Then liposome was co-transplanted with allo-islets via portal vein. The levels of blood glucose and C-peptide were detected daily after transplantation. Also hepatic lymphocytes after transplantation were isolated for determining the proportion of activated cells and signaling pathway changes. Results Artificial liposome could be easily loaded with biotinylated peptide and its diameter was between 50 to 500 nm. Qa-1/PD-L1 liposome could significantly suppress lymphocyte proliferation, activation and secretion of IFN-γ in MLR by an activation of SHP1/2 and an inhibition of Syk pathway. Qa-1/PD-L1 liposomes could suppress the activation of hepatic lymphocytes in vivo by activating SHP1/2, protecting islet allografts and maintaining a normal level of blood glucose in recipients. Conclusions Qa-1/PD-L1 loaded liposome can effectively suppress allograft rejection and improve the outcomes of islet transplantation. Key words: Mouse; Islet transplantation; Qa-1; PD-L1; Graft rejection; SHP1/2