Impact of Donation Mode on the Proportion and Function of T Lymphocytes in the Liver.

Emmanuel Xystrakis,Susan Fuggle,Nigel Heaton,Wayel Jassem,Mohamed Rela,Xiaohong Huang,Alberto Quaglia,Andreas Prachalias,Oltin Tiberiu Pop,Yun Ma,Fang Lin,Muhammed Yuksel,Thomas Gebhardt

doi:10.1371/journal.pone.0139791

Abstract

BackgroundLiver T-cells respond to the inflammatory insult generated during organ procurement and contribute to the injury following reperfusion. The mode of liver donation alters various metabolic and inflammatory pathways but the way it affects intrahepatic T-cells is still unclear.MethodsWe investigated the modifications occurring in the proportion and function of T-cells during liver procurement for transplantation. We isolated hepatic mononuclear cells (HMC) from liver perfusate of living donors (LD) and donors after brain death (DBD) or cardiac death (DCD) and assessed the frequency of T-cell subsets, their cytokine secretion profile and CD8 T-cell cytotoxicity function, responsiveness to a danger associated molecular pattern (High Mobility Group Box1, HMGB1) and association with donor and recipient clinical parameters and immediate graft outcome.ResultsWe found that T-cells in healthy human livers were enriched in memory CD8 T-cells exhibiting a phenotype of non-circulating tissue-associated lymphocytes, functionally dominated by more cytotoxicity and IFN-γ-production in DBD donors, including upon activation by HMGB1 and correlating with peak of post-transplant AST. This liver-specific pattern of CD8 T-cell was prominent in DBD livers compared to DCD and LD livers suggesting that it was influenced by events surrounding brain death, prior to retrieval.ConclusionMode of liver donation can affect liver T-cells with increased liver damage in DBD donors. These findings may be relevant in designing therapeutic strategies aimed at organ optimization prior to transplantation.

Highlights

Liver transplantation is the only treatment for acute and chronic liver failure
We found that T-cells in healthy human livers were enriched in memory CD8 T-cells exhibiting a phenotype of non-circulating tissue-associated lymphocytes, functionally dominated by more cytotoxicity and IFN-γ-production in donors after brain death (DBD) donors, including upon activation by HMGB1 and correlating with peak of post-transplant AST
This liver-specific pattern of CD8 T-cell was prominent in DBD livers compared to donors after cardiac death (DCD) and living donors (LD) livers suggesting that it was influenced by events surrounding brain death, prior to retrieval

Summary

Introduction

The increased demand for organs has led to utilization of marginal donor, which include deceased donors after cardiac death (DCD), older donors and those with abnormal liver biochemistry. Marginal organs are vulnerable and have been seen to be associated with increased rate of graft failure following transplantation [2]. There is increasing evidence that brain death (BD) has a number of sequelae on donor organs, impacting on graft and patient outcome [3]. There is no specific therapy to treat the effects of BD and studies aiming at reducing the level of transaminase and the rate of acute rejection with steroid pre-treatment of the donor did not improve outcomes after liver transplantation [9]

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Conclusion