Hepatic T Cells Derived from Normothemic Machine Perfused Grafts Contained More Regulatory T Cells and Fewer Proinflammatory Cytokines Producing T Cells Than Those from Cold Storage Grafts
1Institute of Liver Studies, King's College London School of Medicine at King's College, London, United Kingdom
Nuffield Department of Surgical Sciences, Oxford University, Oxford, United Kingdom.
Meeting: 2015 American Transplant Congress
Abstract number: A207
Keywords: Liver transplantation
Session Information
Session Name: Poster Session A: Liver: Immunosuppression and Rejection
Session Type: Poster Session
Date: Saturday, May 2, 2015
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Exhibit Hall E
Background & aim:
In liver transplantation, ischemia reperfusion (I/R) injury is associated with an inflammatory response affecting graft and patient outcomes. Ex-vivo normothermic machine perfusion (NMP) of donor allografts prior to transplantation can attenuate I/R injury, leading to improved liver function after implantation and increased utilization of grafts from marginal donors. Livers contain a significant amount of mononuclear cells that are involved in liver damage. To assess the influence of NMP on hepatic inflammation, the phenotype and function of intra-hepatic lymphocytes derived from NMP – versus cold storage (CS) – preserved livers were compared.
Methods: All samples were obtained from liver allografts used for the phase I clinical trial of the Organanox NMP device. Second passage perfusates were collected from 12 grafts donated after brain death (DBD) immediately after NMP and compared to that of 21 CS grafts. Hepatic mononuclear cells (HMC) from the perfusate were isolated by density gradient centrifugation. Flow cytometry was used to define the phenotypes and the proportions of activated cytokine producing HMC.
Results: The mean preservation time was 11.5 hours for NMP and 9.5 hours for CS. Although the frequency of CD4+ T cells, NK and NKT cells were comparable between NMP and CS grafts, the frequency of CD8+ T cells (p=0.01) and CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) (p=0.03) was significantly higher in NMP than in CS liver grafts. The proportions of both CD4+ and CD8+ T cells producing the pro-inflammatory cytokines IFNγ (p=0.008 and p=0.006, respectively) and IL-17 (p=0.001 and p=0.001, respectively) was significantly lower in NMP than in CS grafts. Additionally, there were fewer CD4+ T cells producing IL-2 in NMP versus CS allografts.
Conclusion: These data demonstrate more Tregs and less pro-inflammatory T cells in NMP allografts, as compared to their CS counterparts. Brain death has been previously characterized as a pro-inflammatory state and the utilization of NMP rather than cold storage techniques modulates the allograft inflammatory response. Further studies are warranted to determine if these findings are associated with the improved clinical outcomes.
To cite this abstract in AMA style:
Huang X, Ravikumar R, Coussios C, Srinivasan P, Heaton N, Friend P, Jassem W, Ma Y. Hepatic T Cells Derived from Normothemic Machine Perfused Grafts Contained More Regulatory T Cells and Fewer Proinflammatory Cytokines Producing T Cells Than Those from Cold Storage Grafts [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/hepatic-t-cells-derived-from-normothemic-machine-perfused-grafts-contained-more-regulatory-t-cells-and-fewer-proinflammatory-cytokines-producing-t-cells-than-those-from-cold-storage-grafts/. Accessed May 21, 2025.« Back to 2015 American Transplant Congress