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.