Hypothermic oxygenated machine perfusion influences the immunogenicity of donor livers in humans

Abstract

Hypothermic oxygenated machine perfusion (HOPE) is an organ preservation strategy shown to reduce ischemia-reperfusion injury (IRI)-related complications following liver transplantation. In animal models, HOPE can also decrease alloimmune responses after transplantation, but this remains to be evaluated in humans. Our study, involving 27 patients undergoing liver transplantation enrolled in 2 randomized controlled trials comparing static cold storage with HOPE (14 HOPE-treated and 13 static cold storage-treated), delves into the impact of HOPE on the molecular profile of liver allografts and on the immune responses elicited after transplantation. Following HOPE treatment, fewer intrahepatic immune cells were observed in liver perfusates compared to static cold storage. Analysis of liver tissue transcriptome at reperfusion revealed an effect of HOPE on the reactive oxygen species pathway. Two weeks after transplantation, HOPE recipients exhibited increased circulating CD4+FOXP3+CD127lo regulatory T cells ( p < 0.01), which corresponded to a higher frequency of donor-specific regulatory T cells ( p < 0.01) and was followed by reduced alloreactivity index of CD8+ T cells 3 months after transplant. Our study provides novel mechanistic insight into the capacity of HOPE to influence liver ischemia-reperfusion injury and to modulate effector and regulatory donor-specific T-cell responses after transplantation. These findings, which confirm observations made in animal models, help explain the decreased rejection rates reported in patients receiving HOPE-treated allografts.