Donor MHC-specific thymus vaccination allows for immunocompatible allotransplantation  

作　　者：Yang Liu Hexi Feng Ke Li Ruiyi Li Xiao-Jie Zhang Ye Tian Yujiang Fang Yanjie Zhou Ling Liu Xiaoqing Zhang 

机构地区：[1]Translational Medical Center for Stem Cell Therapy,Shanghai East Hospital,School of Medicine,Tongji University,Shanghai,China [2]Translational Research Institute of Brain and Brain-Like Intelligence,Shanghai Fourth People’s Hospital,School of Medicine,Tongji University,Shanghai,China [3]Shanghai Institute of Stem Cell Research and Clinical Translation,Shanghai,China [4]Stem Cell Research Center and Key Laboratory of Neuroregeneration of Shanghai Universities,School of Medicine,Tongji University,Shanghai,China [5]Clinical Center for Brain and Spinal Cord Research,Tongji University,Shanghai,China [6]Department of Gynaecology,Jing’an District Hospital of Traditional Chinese Medicine,Shanghai,China [7]School of Foreign Studies,Tongji University,Shanghai,China [8]Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education,Orthopaedic Department of Tongji Hospital,Shanghai,China

出　　处：《Cell Research》2025年第2期132-144,共13页细胞研究(英文版)

基　　金：supported by grants from the National Natural Science Foundation of China(82025020,82230072 and 32270874);the National Key R&D Program of China(2021YFA1100400 and 2021YFC2701400);the Science and Technology Commission of Shanghai Municipality(21140902300 and 22ZR1464000);Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone(ZJ2018-ZD-004);Medical Research Project of Jing’an District,Shanghai(2023ZX03);Shanghai Municipal Health Commission(202240011);Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai;sponsored by Shanghai Blue Cross Brain Hospital Co.,Ltd.,and Shanghai Tongji University Education Development Foundation.

摘　　要：Organ transplantation is the last-resort option to treat organ failure.However,less than 10%of patients benefit from this only option due to lack of major histocompatibility complex(MHC)-matched donor organs and 25%–80%of donated organs could not find MHC-matched recipients.T cell allorecognition is the principal mechanism for allogeneic graft rejection.We herein present a“donor MHC-specific thymus vaccination”(DMTV)strategy to induce T cell tolerance to both autologous and allogeneic donor MHC.Allogeneic MHC molecules were expressed in the recipient thymus through adeno-associated virus-mediated delivery,which led to stable expression of allogeneic MHC together with the autologous MHC in the engineered thymus.During local T cell education,those T cells recognizing either autologous MHC or allogeneic MHC were equally depleted.We constructed C57BL/6-MHC and BALB/c-MHC dual immunocompatible mice via thymus vaccination of C57BL/6-MHC into the BALB/c thymus and observed longterm graft tolerance after transplantation of C57BL/6 skin and C57BL/6 mouse embryonic stem cells into the vaccinated BALB/c mice.We also validated our DMTV strategy in a bone marrow,liver,thymus(BLT)-humanized mouse model for immunocompatible allotransplantation of human embryonic stem cells.Our study suggests that the DMTV strategy is a potent avenue to introduce a donor compatible immune system in recipients,which overcomes the clinical dilemma of the extreme shortage of MHC-matched donor organs for treating patients with end-stage organ failure.

关 键 词：VACCINATION ORGANS DONOR 

分 类 号：R73[医药卫生—肿瘤]