dwyer-livergrafts-2013.pdf (728.75 kB)
Liver grafts from CD39-overexpressing rodents are protected from ischemia reperfusion injury due to reduced numbers of resident CD4+ T cells
journal contributionposted on 2013-04-01, 00:00 authored by Sandra Pommey, Bo Lu, Jennifer McRae, John Stagg, Prue Hill, Evelyn Salvaris, Simon C Robson, Anthony J F d'Apice, Peter J Cowan, Karen DwyerKaren Dwyer
UNLABELLED: Ischemia-reperfusion injury (IRI) is a major limiting event for successful liver transplantation, and CD4+ T cells and invariant natural killer T (iNKT) cells have been implicated in promoting IRI. We hypothesized that hepatic overexpression of CD39, an ectonucleotidase with antiinflammatory functions, will protect liver grafts after prolonged cold ischemia. CD39-transgenic (CD39tg) and wildtype (WT) mouse livers were transplanted into WT recipients after 18 hours cold storage and pathological analysis was performed 6 hours after transplantation. Serum levels of alanine aminotransferase and interleukin (IL)-6 were significantly reduced in recipients of CD39tg livers compared to recipients of WT livers. Furthermore, less severe histopathological injury was demonstrated in the CD39tg grafts. Immune analysis revealed that CD4+ T cells and iNKT cells were significantly decreased in number in the livers of untreated CD39tg mice. This was associated with a peripheral CD4+ T cell lymphopenia due to defective thymocyte maturation. To assess the relative importance of liver-resident CD4+ T cells and iNKT cells in mediating liver injury following extended cold preservation and transplantation, WT mice depleted of CD4+ T cells or mice genetically deficient in iNKT cells were used as donors. The absence of CD4+ T cells, but not iNKT cells, protected liver grafts from early IRI. CONCLUSION: Hepatic CD4+ T cells, but not iNKT cells, play a critical role in early IRI following extended cold preservation in a liver transplant model.
Pagination1597 - 1606
Publication classificationC1 Refereed article in a scholarly journal
Copyright notice2013, Wiley
Alanine TransaminaseAnimalsAntigens, CDApyraseCD4-Positive T-LymphocytesDisease Models, AnimalInterleukin-6Killer Cells, NaturalLiver TransplantationLymphopeniaMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicReperfusion InjuryT-Lymphocytes, RegulatoryUp-RegulationScience & TechnologyLife Sciences & BiomedicineGastroenterology & HepatologyHEPATIC ISCHEMIA\/REPERFUSION INJURYA(2A) RECEPTOR ACTIVATIONIMMUNE SUPPRESSIONHUMAN CD39IFN-GAMMAADENOSINETRANSPLANTATIONINFLAMMATIONLYMPHOCYTESImmunology