title: Augmentation of Recipient Adaptive Alloimmunity by Donor Passenger Lymphocytes within the Transplant.
abstract: Chronic rejection of solid organ allografts remains the major cause of transplant failure. Donor-derived tissue-resident lymphocytes are transferred to the recipient during transplantation, but their impact on alloimmunity is unknown. Using mouse cardiac transplant models, we show that graft-versus-host recognition by passenger donor CD4 T cells markedly augments recipient cellular and humoral alloimmunity, resulting in more severe allograft vasculopathy and early graft failure. This augmentation is enhanced when donors were pre-sensitized to the recipient, is dependent upon avoidance of host NK cell recognition, and is partly due to provision of cognate help for allo-specific B cells from donor CD4 T cells recognizing B cell MHC class II in a peptide-degenerate manner. Passenger donor lymphocytes may therefore influence recipient alloimmune responses and represent a therapeutic target in solid organ transplantation.
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Ines G
authors.initials: IG
authors.lastname: Harper
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Ali
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Simon J F
authors.initials: SJ
authors.lastname: Harper
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wlodek
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Jawaher
authors.initials: J
authors.lastname: Alsughayyir
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Negus
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: M Saeed
authors.initials: MS
authors.lastname: Qureshi
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Reza
authors.initials: R
authors.lastname: Motalleb-Zadeh
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Kourosh
authors.initials: K
authors.lastname: Saeb-Parsy
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Bolton
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Bradley
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Menna R
authors.initials: MR
authors.lastname: Clatworthy
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Conlon
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK. Electronic address: gjp25@cam.ac.uk.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Pettigrew
mesh_terms: D056704:Adaptive Immunity; D064591:Allografts / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D006084:Graft Rejection / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D056724:Immunity, Humoral / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D010455:Peptides / Q000378:metabolism; D010950:Plasma Cells / Q000473:pathology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011947:Receptors, Antigen, B-Cell