Recent Advances in Costimulatory Blockade to Induce Immune Tolerance in Liver Transplantation

Mingjie Ding,Shuijun Zhang,Wenzhi Guo,Yuting He

doi:10.3389/fimmu.2021.537079

Mingjie Ding, Shuijun Zhang + Show 2 more

Open Access

https://doi.org/10.3389/fimmu.2021.537079

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Abstract

Liver transplantation is an effective therapy for end-stage liver disease. However, most postoperative patients must take immunosuppressive drugs to prevent organ rejection. Interestingly, some transplant recipients have normal liver function and do not experience organ rejection after the withdrawal of immunosuppressive agents. This phenomenon, called immune tolerance, is the ultimate goal in clinical transplantation. Costimulatory molecules play important roles in T cell-mediated immune responses and the maintenance of T cell tolerance. Blocking costimulatory pathways can alter T cell responses and prolong graft survival. Better understanding of the roles of costimulatory molecules has facilitated the use of costimulatory blockade to effectively induce immune tolerance in animal transplantation models. In this article, we review the state of the art in costimulatory pathway blockade for the induction of immune tolerance in transplantation and its potential application prospects for liver transplantation.

Highlights

Liver transplantation is the most effective treatment for end-stage liver disease
The relative strength of the costimulatory and coinhibitory signals activated after transplant determines how T cells respond to allografts
As the key second signal, costimulatory pathways are essential in the activation of T cells, especially CD28/ B7 costimulatory signal pathway

Summary

Introduction

Liver transplantation is the most effective treatment for end-stage liver disease. graft rejection seriously restricts graft function and recipient quality of life. As blocking these second signals can prevent T cell activation and acute rejection, costimulatory blockade is currently one of the most active areas of research in transplantation immunity. Blocking costimulatory pathways during liver transplantation may change anti-allograft immune responses and weaken rejection, and it is may be a strategy to induce immune tolerance in transplant recipients, thereby limiting toxicity from immunosuppressive drugs after transplantation [18].

Results

Conclusion