Investigating a Novel Cellular Therapy to Prevent and Treat Acute Antibody Mediated Kidney Transplant Rejection

项目摘要 移植特异性抗体(同种抗体)可介导急性抗体介导的排斥反应(Amr)。 而且对移植肾的长期存活期也有负面影响。我们小组发现了一种 抑制移植后同种异体抗体产生的新的调节性CD8 T细胞亚群。我们指的是 这些抗体抑制CD8 T细胞作为CD8标签支持细胞，并已开发出一种策略，以增强其 在体内发育中，将其表型与其他异位基因修饰的CD8 T细胞区分开来，并在体外评估其 和体内功能。在目标1中，我们将进行临床前研究，以研究CD8标签支持的疗效。 预防肾移植后同种异体抗体和AMR发生的细胞 复制人肾AMR组织病理学的小鼠肾移植模型 移植受者。在目标2中，我们将进行临床前研究，以调查过继细胞的疗效。 CD8Tab-Supp细胞治疗AMR，延长肾移植功能和存活时间。我们的研究 团队汇集了具有临床移植、移植免疫学、显微外科专业知识的研究人员 肾脏组织病理学检查。

Project Summary Transplant specific antibodies (alloantibodies) are known to mediate acute antibody-mediated rejection (AMR) after kidney transplant and also negatively impact long-term kidney allograft survival. Our group discovered a novel regulatory CD8+ T cell subset which suppresses alloantibody production posttransplant. We refer to these antibody suppressor CD8+ T cells as CD8+ TAb-supp cells and have developed a strategy to enhance their in vivo development, distinguish their phenotype from other alloprimed CD8+ T cells and assess their in vitro and in vivo function. In Aim 1 we will perform pre-clinical studies to investigate the efficacy of CD8+ TAb-supp cells to prevent the development of de novo post-transplant alloantibody and AMR after kidney transplant using a murine model of kidney transplant which reproduces the histopathology of AMR observed in human kidney transplant recipients. In Aim 2 we will perform pre-clinical studies to investigate the efficacy of adoptive cellular therapy with CD8+ TAb-supp cells to treat AMR and prolong kidney transplant function and survival. Our research team assembles investigators with expertise in clinical transplantation, transplant immunology, microsurgery and kidney histopathology.