title: Impact of Donation Mode on the Proportion and Function of T Lymphocytes in the Liver.
abstract: BACKGROUND
  Liver 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  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 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.
  
  
  CONCLUSIONS
  Mode 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.
authors.affiliation: Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London at King's College Hospital, London, United Kingdom.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Xystrakis
authors.affiliation: Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London at King's College Hospital, London, United Kingdom.
authors.forename: Muhammed
authors.initials: M
authors.lastname: Yuksel
authors.affiliation: Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London at King's College Hospital, London, United Kingdom.
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.affiliation: Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London at King's College Hospital, London, United Kingdom.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Huang
authors.affiliation: Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London at King's College Hospital, London, United Kingdom.
authors.forename: Oltin Tiberiu
authors.initials: OT
authors.lastname: Pop
authors.affiliation: Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London at King's College Hospital, London, United Kingdom.
authors.forename: Alberto
authors.initials: A
authors.lastname: Quaglia
authors.affiliation: Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London at King's College Hospital, London, United Kingdom.
authors.forename: Nigel
authors.initials: N
authors.lastname: Heaton
authors.affiliation: Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London at King's College Hospital, London, United Kingdom.
authors.forename: Andreas
authors.initials: A
authors.lastname: Prachalias
authors.affiliation: Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London at King's College Hospital, London, United Kingdom.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Rela
authors.affiliation: Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Susan
authors.initials: S
authors.lastname: Fuggle
authors.affiliation: Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London at King's College Hospital, London, United Kingdom.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London at King's College Hospital, London, United Kingdom.
authors.forename: Wayel
authors.initials: W
authors.lastname: Jassem
mesh_terms: D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008099:Liver / Q000276:immunology* / Q000378:metabolism*; D016031:Liver Transplantation; D008875:Middle Aged; D010477:Perfusion; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014019:Tissue Donors; D009927:Tissue and Organ Procurement; D066027:Transplant Recipients; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D024243:HMGB1 Protein