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Differential migration of passenger leukocytes and rapid deletion of naive alloreactive CD8 T cells after mouse liver transplantation
journal contribution
posted on 2013-11-01, 00:00 authored by Szun S Tay, Bo Lu, Fred Sierro, Volker Benseler, Claire M McGuffog, G Alex Bishop, Peter J Cowan, Geoffrey W McCaughan, Karen DwyerKaren Dwyer, David G Bowen, Patrick BertolinoDonor passenger leukocytes (PLs) from transplanted livers migrate to recipient lymphoid tissues, where they are thought to induce the deletion of donor-specific T cells and tolerance. Difficulties in tracking alloreactive T cells and PLs in rats and in performing this complex surgery in mice have limited progress in identifying the contribution of PL subsets and sites and the kinetics of T cell deletion. Here we developed a mouse liver transplant model in which PLs, recipient cells, and a reporter population of transgenic CD8 T cells specific for the graft could be easily distinguished and quantified in allografts and recipient organs by flow cytometry. All PL subsets circulated rapidly via the blood as soon as 1.5 hours after transplantation. By 24 hours, PLs were distributed differently in the lymph nodes and spleen, whereas donor natural killer and natural killer T cells remained in the liver and blood. Reporter T cells were activated in both liver and lymphoid tissues, but their numbers dramatically decreased within the first 48 hours. These results provide the first unequivocal demonstration of the differential recirculation of liver PL subsets after transplantation, and show that alloreactive CD8 T cells are deleted more rapidly than initially reported. This model will be useful for dissecting early events leading to the spontaneous acceptance of liver transplants.
History
Journal
Liver transplantationVolume
19Issue
11Pagination
1224 - 1235Publisher
WileyLocation
London, Eng.Publisher DOI
eISSN
1527-6473Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2013, American Association for the Study of Liver DiseasesUsage metrics
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No categories selectedKeywords
AllograftsAnimalsCD8-Positive T-LymphocytesCell MovementLeukocytesLiver TransplantationLymphocyte ActivationMaleMice, Inbred C57BLNatural Killer T-CellsTissue DonorsScience & TechnologyLife Sciences & BiomedicineGastroenterology & HepatologySurgeryTransplantationDENDRITIC CELLSNATURAL-KILLERSPONTANEOUS ACCEPTANCESPONTANEOUS TOLERANCEALLOGRAFT ACCEPTANCEMICEACTIVATIONREJECTIONRATSIMMUNOSUPPRESSION
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