Abstract
Kidney transplantation is the most common solid organ transplant and the best current therapy for end-stage kidney failure. However, with standard immunosuppression, most transplants develop chronic dysfunction or fail, much of which is due to chronic immune injury. Tregs are a subset of T cells involved in limiting immune activation and preventing autoimmune disease. These cells offer the potential to provide tolerance or to allow reduction in immunosuppression in kidney transplants. The importance of Tregs in kidney transplantation has been shown in a number of seminal mouse and animal studies, including those with T cell receptors (TCRs) transgenic Tregs (TCR-Tregs) or Chimeric Antigen Receptor (CAR) Tregs (CAR-Tregs) showing that specificity increases the potency of Treg function. Here we outline the animal and human studies and clinical trials directed at using Tregs in kidney transplantation and other tolerance settings and the various modifications to enhance allo-specific Treg function in vivo and in vitro.
Highlights
Kidney transplantation is currently the preferred treatment for patients with end-stage kidney disease (ESKD)
We focus primarily on antigen specific Tregs induction in kidney transplantation tolerance and other tolerance studies in animal models and human studies of kidney transplantation and discuss several approaches to generate and expand antigen specific Tregs which can protect against transplant rejection
The safety of infusing mildly manipulated Tregs has been demonstrated in clinical trials of kidney transplantation
Summary
Kidney transplantation is currently the preferred treatment for patients with end-stage kidney disease (ESKD). The primary limitation of long-term kidney allograft survival has been chronic immune-mediated rejection. This is due to both cellular and humoral pathways as well as innate immune factors and possibly other pathways. A number of bone marrow-based strategies creating temporary or permanent donor hematopoietic chimerism have reached clinical trials. The first of these was done at Massachusetts General Hospital (MGH), followed closely by Stanford, John Hopkins and North Western [2,3,4,5,6]. A number of cell types with immune-regulatory function have been characterized as Tregs, though the one best understood, at present, are the CD4+FOXP3+
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