Ex vivo anchored PD-L1 functionally prevent in vivo renal allograft rejection

Organ transplantation is the optimal treatment for patients with end-stage diseases. T cell activation is a major contributing factor toward the trigger of rejection. Induction therapy with T cell depleting agent is a common option but increases the risk of severe systemic infections. The ideal therapy should precisely target the allograft. Here, we developed a membrane-anchored-protein PD-L1 (map-PD-L1), which effectively anchored onto the surface of rat glomerular endothelial cells (rgEC). The expression of PD-L1 increased directly with map-PD-L1 concentration and incubation time. Moreover, map-PD-L1 was even stably anchored to rgEC at low temperature. Map-PD-L1 could bind to PD-1 and significantly promote T cell apoptosis and inhibited T cell activation. Using kidney transplantation models, we found that ex vivo perfusion of donor kidneys with map-PD-L1 significantly protected grafts against acute injury without using any immunosuppressant. We found map-PD-L1 could reduce T cell graft infiltration and increase intragraft Treg infiltration, suggesting a long-term effect in allograft protection. More importantly, modifying donor organs in vitro was not only safe, but also significantly reduced the side effects of systemic application. Our results suggested that ex vivo perfusion of donor organ with map-PD-L1 might provide a viable clinical option for organ-targeted induction therapy in organ transplantation.

Automated summary

This study developed a membrane-anchored protein PD-L1 (map-PD-L1) that can precisely target the allograft in organ transplantation. The results showed that map-PD-L1 can protect grafts against acute injury and reduce T cell graft infiltration, potentially providing a long-term effect in allograft protection.