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

oleh: Ines G. Harper, Jason M. Ali, Simon J.F. Harper, Elizabeth Wlodek, Jawaher Alsughayyir, Margaret C. Negus, M. Saeed Qureshi, Reza Motalleb-Zadeh, Kourosh Saeb-Parsy, Eleanor M. Bolton, J. Andrew Bradley, Menna R. Clatworthy, Thomas M. Conlon, Gavin J. Pettigrew

Format: Article
Diterbitkan: Elsevier 2016-05-01

Deskripsi

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.