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

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

来源：Cell Reports, 2016, 15(6): 1214-1227.

DOI：10.1016/j.celrep.2016.04.009

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.

• 出版日期2016-5-10