Li Tong, Zhang Wenqian, Xu Qing, Li Shentao, Tong Xuehong, Ding Jie, Li Hui, Hou Shengcai, Xu Zhidong, Jablons David M, You Liang
Thoracic Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Thoracic Oncology Laboratory, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143-1724, USA.
Exp Ther Med. 2018 Jun;15(6):4961-4971. doi: 10.3892/etm.2018.6058. Epub 2018 Apr 13.
Donor organ rejection remains a significant problem. The present study aimed to assess whether transferring a donor's major histocompatibility complex (MHC) genes to the recipient could mitigate rejection in organ transplantation. Seven loci of MHC genes from donor mice were amplified and ligated into vectors; the vectors either contained one K locus, seven loci or were empty (control). The vectors were subsequently injected into the thymus of recipients (in heterotransplants, recipient rats received the vector containing one K locus), following which donor mouse hearts were transplanted. Following the transplantation of allograft and heterograft, electrocardiosignals were viable for a significantly longer duration in recipient mice and rats receiving the donor histocompatibility-2 complex (H-2) genes compared with those in controls, and in mice that received seven vectors compared with those receiving one vector. Mixed lymphocyte cultures containing cells from these recipients proliferated significantly less compared with mixed lymphocyte cultures containing controls. Also, hearts from H-2 genes-treated recipients demonstrated less lymphocyte infiltration and necrosis compared with the control recipient. The present study concluded that allograft and heterograft rejection may be mitigated by introducing the donor's MHC into the recipient; transferring seven loci has been demonstrated to be more effective than transferring one locus.
供体器官排斥仍然是一个重大问题。本研究旨在评估将供体的主要组织相容性复合体(MHC)基因转移到受体是否可以减轻器官移植中的排斥反应。从小鼠供体中扩增出七个MHC基因位点,并连接到载体中;这些载体要么包含一个K位点、七个位点,要么为空载体(对照)。随后将这些载体注射到受体的胸腺中(在异种移植中,受体大鼠接受含有一个K位点的载体),之后移植供体小鼠的心脏。在同种异体移植和异种移植后,与对照组相比,接受供体组织相容性-2复合体(H-2)基因的受体小鼠和大鼠的心电图信号存活时间显著更长,并且与接受一个载体的小鼠相比,接受七个载体的小鼠的心电图信号存活时间更长。与含有对照细胞的混合淋巴细胞培养物相比,含有这些受体细胞的混合淋巴细胞培养物增殖明显较少。此外,与对照受体相比,接受H-2基因治疗的受体的心脏表现出较少的淋巴细胞浸润和坏死。本研究得出结论,通过将供体的MHC引入受体可以减轻同种异体移植和异种移植排斥反应;已证明转移七个位点比转移一个位点更有效。