Programmed death-1 ligand-1 (PD-L1, CD274, B7-H1) has been identified as the ligand for the immunoinhibitory receptor programmed death-1 and has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. In this study, we tested the effect of PD-L1-transfected pancreatic beta-cell line established from a transgenic NDD/Lt mouse (NIT) on the alloresponse and streptozotocin-induced diabetes.Methods.
The diabetes model was established by a low dose of streptozotocin in Balb/C mice. PD-L1 transfected NIT cell line was established, namely NIT-PD-L1. NIT-1, empty vector-transfected NIT-1, or NIT-PD-L1 cells were transplanted into diabetic mice by intraperitoneal injection, respectively. Proliferation and apoptosis of splenic lymphocytes were detected by labeling with carboxy fluoroscein succinimidyl ester or AnnexinV-Cy5 and proliferation index (PI). Cytokines were determined by enzyme-linked immunosorbent assay and flow cytometry analysis.Results.
When compared with the controls, overexpression of PD-L1 on NIT-1 cells markedly prolonged allograft survival in diabetic mice. In mixed cells reaction, splenic lymphocytes from NIT-PD-L1-transplanted diabetic mice co-culture with mitomycin C-treated NIT-PD-L1 showed the lowest proliferative response but severe apoptosis. In addition, NIT-PD-L1 suppressed interferon-γ but up-regulated interleukin-4 and -10 productions by those lymphocytes in vitro and in vivo.Conclusion.
Our data demonstrated that overexpression of PD-L1 on pancreatic β cells significantly can prolong allograft survival, and it is associated with inhibition of lymphocytes activation and proliferation, induction of lymphocytes apoptosis.