First Author | Ma D | Year | 2016 |
Journal | PLoS One | Volume | 11 |
Issue | 3 | Pages | e0152087 |
PubMed ID | 26990974 | Mgi Jnum | J:251706 |
Mgi Id | MGI:6092897 | Doi | 10.1371/journal.pone.0152087 |
Citation | Ma D, et al. (2016) PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice. PLoS One 11(3):e0152087 |
abstractText | BACKGROUND: Islet transplantation may potentially cure type 1 diabetes mellitus (T1DM). However, immune rejection, especially that induced by the alloreactive T-cell response, remains a restraining factor for the long-term survival of grafted islets. Programmed death ligand-1 (PD-L1) is a negative costimulatory molecule. PD-L1 deficiency within the donor heart accelerates allograft rejection. Here, we investigate whether PD-L1 deficiency in donor islets reduces allograft survival time. METHODS: Glucose Stimulation Assays were performed to evaluate whether PD-L1 deficiency has detrimental effects on islet function. Islets isolated from PDL1-deficient mice or wild- type (WT) mice (C57BL/6j) were implanted beneath the renal capsule of streptozotocin (STZ)-induced diabetic BALB/c mice. Blood glucose levels and graft survival time after transplantation were monitored. Moreover, we analyzed the residual islets, infiltrating immune cells and alloreactive cells from the recipients. RESULTS: PD-L1 deficiency within islets does not affect islet function. However, islet PD-L1 deficiency increased allograft rejection and was associated with enhanced inflammatory cell infiltration and recipient T-cell alloreactivity. CONCLUSIONS: This is the first report to demonstrate that PD-L1 deficiency accelerated islet allograft rejection and regulated recipient alloimmune responses. |