Deakin University
Browse

File(s) under permanent embargo

Differential migration of passenger leukocytes and rapid deletion of naive alloreactive CD8 T cells after mouse liver transplantation

Version 2 2024-06-03, 18:12
Version 1 2018-07-10, 10:47
journal contribution
posted on 2024-06-03, 18:12 authored by Szun S Tay, Bo Lu, Fred Sierro, Volker Benseler, Claire M McGuffog, G Alex Bishop, Peter J Cowan, Geoffrey W McCaughan, Karen M Dwyer, David G Bowen, Patrick Bertolino
Donor 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 transplantation

Volume

19

Pagination

1224-1235

Location

London, Eng.

eISSN

1527-6473

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2013, American Association for the Study of Liver Diseases

Issue

11

Publisher

Wiley