Impact of donation mode on the proportion and function of T lymphocytes in the liver : WestminsterResearch

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Title	Impact of donation mode on the proportion and function of T lymphocytes in the liver
Type	Journal article
Authors	Xystrakis, E., Yuksel, M., Lin, F., Huang, X., Pop, O.T., Quaglia, A., Heaton, N., Prachalias, A., Rela, M., Fuggle, S., Ma, Y. and Jassem, W.
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. Conclusion 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.
Article number	e0139791
Journal	PLoS ONE
Journal citation	10 (10)
ISSN	1932-6203
Year	2015
Publisher	Public Library of Science
Publisher's version	file (23).pdf License CC BY 4.0 File Access Level Open (open metadata and files)
Digital Object Identifier (DOI)	https://doi.org/10.1371/journal.pone.0139791
Published	29 Oct 2015

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Impact of donation mode on the proportion and function of T lymphocytes in the liver

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