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

项目概要 已知移植特异性抗体（同种抗体）可介导急性抗体介导的排斥反应 (AMR) 肾移植后，也会对同种异体肾的长期存活产生负面影响。我们小组发现了一个 新型调节性 CD8 T 细胞亚群可抑制移植后同种抗体的产生。我们参考 这些抗体抑制性 CD8 T 细胞作为 CD8 Tab-supp 细胞，并开发了一种策略来增强其 体内发育，区分其表型与其他同种异体 CD8 T 细胞并评估其体外 和体内功能。在目标 1 中，我们将进行临床前研究以研究 CD8 TAb-supp 的功效 使用细胞预防肾移植后新发移植后同种抗体和 AMR 的发展 小鼠肾移植模型，再现了在人类肾脏中观察到的 AMR 组织病理学 移植受者。在目标 2 中，我们将进行临床前研究，以调查过继细胞的功效 使用 CD8 Tab-supp 细胞治疗 AMR 并延长肾移植功能和生存期。我们的研究 团队汇集了临床移植、移植免疫学、显微外科专业知识的研究人员 和肾脏组织病理学。

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.