Assessment of donor compatibility in human solid organ transplantation and evaluation of allogeneic responses using a novel humanized mouse model.

Abstract The end result of solid organ transplantation is dictated by selection a well-matched donor, leading to allograft survival. An allogeneic immune response the main immunological barrier for successful transplantation. Donor and recipient human leukocyte antigen (HLA) mismatching results in poor graft acceptance, inflammation rejection. current evaluations donor-recipient HLA incompatibility does not provide adequate information on immunogenicity individual mismatches impact non-HLA-related alloantigens, especially vivo. Here we demonstrate novel method analysis alloimmune responsiveness between donor vivoby introducing humanized mouse model. Using molecular, cellular, genomic analyses, demonstrated that recipient’s personalized provided most sensitive assessment potential donors. In our study, typing mixed lymphocyte reaction (MLR) was indistinguishable 2 related donors recipient. Contrastingly model, selected induced strongest with increased infiltration cytotoxic GzmB +CD8 +T cells. Moreover, same upregulation genes involved rejection identified transcriptomic infiltrating CD45 +cells. Humanized model determined lowest degree recipient-donor response, allowing better minimized risk This approach can be used evaluate alloresponses cell based therapies as well. study supported research funding from Carlos Marguerite Mason Trust, U.S. National Institutes Health, Cancer Institute Grant CA 172230