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.
Preview |
Text
1-s2.0-S2211124716304089-main.pdf - Published Version Download (3MB) | Preview |
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.
Archive Staff Only
 |
View Item |
