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

Hypothermic oxygenated machine perfusion (HOPE) is an organ preservation strategy shown to reduce ischemia-reperfusion-injury (IRI)-related complications following liver transplantation this remains to be evaluated in humans. Analysis of liver tissue transcriptome at reperfusion revealed an effect of HOPE on the reactive oxygen species pathway. Two weeks post transplantation, HOPE recipients exhibited increased circulating CD4+FOXP3+CD127lo regulatory T cells (Tregs) (p<0.01), which corresponded to a higher frequency of donor specific Tregs (p<0.01) and was followed by reduced alloreactivity index of CD8+ T cells 3 months post-transplant. Our study provides novel mechanistic insight into the capacity of HOPE to influence liver IRI and to modulate effector and regulatory donor-specific Tcell responses post-transplantation. These findings, which confirm observations made in animal models, help explain the decreased rejection rates reported in patients receiving HOPE-treated allografts. Overall design: Donors after brain death (DBD) Liver biopsies from 9 cryopreserved liver tissue samples [cold] ( before vs after) and 7 Hypothermic oxygenated machine perfusion [machine] (HOPE)