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Augmentation of Recipient Adaptive Alloimmunity by Donor Passenger Lymphocytes within the Transplant

Harper, IG; Ali, JM; Harper, SJF; Wlodek, E; Alsughayyir, J; Negus, MC; Qureshi, MS; ... Pettigrew, GJ; + view all (2016) Augmentation of Recipient Adaptive Alloimmunity by Donor Passenger Lymphocytes within the Transplant. Cell Reports , 15 (6) pp. 1214-1227. 10.1016/j.celrep.2016.04.009. Green open access

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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.

Type: Article
Title: Augmentation of Recipient Adaptive Alloimmunity by Donor Passenger Lymphocytes within the Transplant
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2016.04.009
Publisher version: http://doi.org/10.1016/j.celrep.2016.04.009
Language: English
Additional information: © 2016 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/1574620
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