title: Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion.
abstract: Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLP-reduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection.
authors.affiliation: The Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, UK.|The Transplant Centre, University Hospital of South Manchester, Manchester, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Stone
authors.affiliation: The Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, UK.|The Transplant Centre, University Hospital of South Manchester, Manchester, UK.
authors.forename: W R
authors.initials: WR
authors.lastname: Critchley
authors.affiliation: The Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, UK.|The Transplant Centre, University Hospital of South Manchester, Manchester, UK.
authors.forename: T
authors.initials: T
authors.lastname: Major
authors.affiliation: The Transplant Centre, University Hospital of South Manchester, Manchester, UK.
authors.forename: G
authors.initials: G
authors.lastname: Rajan
authors.affiliation: Department of Pathology, Institute of Clinical Medicine, University of Oslo, Rikshospitalet, Oslo, Norway.
authors.forename: I
authors.initials: I
authors.lastname: Risnes
authors.affiliation: Department of Pathology, Institute of Clinical Medicine, University of Oslo, Rikshospitalet, Oslo, Norway.
authors.forename: H
authors.initials: H
authors.lastname: Scott
authors.affiliation: Department of Cardiothoracic Surgery, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Q
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Department of Cardiothoracic Surgery, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Wohlfart
authors.affiliation: Department of Cardiothoracic Surgery, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Sjöberg
authors.affiliation: The Transplant Centre, University Hospital of South Manchester, Manchester, UK.
authors.forename: N
authors.initials: N
authors.lastname: Yonan
authors.affiliation: Department of Cardiothoracic Surgery, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Steen
authors.affiliation: The Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, UK.|The Transplant Centre, University Hospital of South Manchester, Manchester, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Fildes
mesh_terms: D000818:Animals; D005260:Female; D007249:Inflammation / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology* / Q000601:surgery; D016040:Lung Transplantation; D008297:Male; D010477:Perfusion; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors