title: Withdrawal of immunosuppression in liver transplantation and the mechanism of tolerance.
abstract: BACKGROUND
  Immunosuppression reagents have side effects and cause considerable long-term morbidity and mortality in patients after liver transplantation. Sufficient evidences showed that minimization or withdrawal of immunosuppression reagents does not deteriorate the recipient's immune response and physiological function and therefore, is feasible in some recipients of liver transplantation. However, the mechanisms are not clear. The present review was to update the current status of immunosuppression in liver transplantation and the mechanism of minimization or withdrawal of immunosuppression in liver recipients.
  
  
  METHODS
  We searched articles in English on minimization or withdrawal of immunosuppression in liver transplantation in PubMed. We focused on the basic mechanisms of immune tolerance in liver transplantation. Studies on immunosuppression minimization or withdrawal protocols and biomarker in tolerant recipients were also analyzed.
  
  
  RESULTS
  Minimization or withdrawal of immunosuppression can be achieved by the induction of immune tolerance, which may not be permanent and can be affected by various factors. However, accurately evaluating immune status post-transplant is a prerequisite to achieve individualized immunosuppression. Numerous mechanisms for immune tolerance have been found, including immunophenotypic shift of memory CD8+ T cells and CD4+ T cell subsets. Activation of the inflammasome through apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) in dendritic cells is associated with rejection after liver transplantation.
  
  
  CONCLUSIONS
  Minimization or withdrawal of immunosuppression can be achieved by the induction of immune tolerance via different mechanisms. This process could be affected by immunophenotypic shift of memory CD8+ T cells and CD4+ T cell subsets, which may be correlated with activation of the inflammasome through ASC in dendritic cells.
authors.affiliation: Institute of Hepatobiliary and Pancreatic Diseases, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhengzhou University, School of Medicine, Zhengzhou 450052, China. ylsun@zzu.edu.cn.
authors.forename: Chi-Xian
authors.initials: CX
authors.lastname: Zhang
authors.forename: Pei-Hao
authors.initials: PH
authors.lastname: Wen
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Sun
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D058847:Inflammasomes / Q000276:immunology; D016031:Liver Transplantation; D028761:Withholding Treatment
chemical_list: D007166:Immunosuppressive Agents; D058847:Inflammasomes