title: Current understanding of alloimmunity of the intestinal graft.
abstract: OBJECTIVE
  This review focuses on the known mechanisms of alloimmunity that occur after transplantation and what is being done in order to improve graft and patient survival, particularly in the long term.
  
  
  RESULTS
  The presence of mismatched antigens and epitopes might relate directly to the development of de-novo donor-specific antibodies (DSA), and thus, rejection. In an abdominal wall transplant, the skin graft could be the first to show signs of rejection. The epithelial or endothelial cells are the main targets in acute and chronic rejection, respectively. Possible therapeutical targets are gut homing T cells and cells of the innate immune system. Chimerism development might mostly occur in isolated lymph nodes, but also in the epithelium, particularly after transplantation of bone marrow mesenchymal stromal cells.
  
  
  CONCLUSIONS
  Ischemia-reperfusion, surgical injury, and bacterial translocation trigger the innate immune system, starting acute rejection. Interaction between donor and recipient immune cells generate injury and tolerance, which occur mostly in secondary lymphoid organs, lamina propria, and epithelium. Chronic rejection mostly affects the endothelial cells, generating graft dysfunction. DSA increase the risk of graft rejection both acutely and chronically, and the liver protects against their effects. Induction therapies deplete lymphocytes prior to implantation, and maintenance therapies inhibit T-cell expansion. Rejection rates are the lowest when depleting drugs and a combination of interleukin 2 receptor blockade, inhibition of T-cell expansion, and steroids are used as maintenance therapy. Chimerism and tolerogenic regiments that induce Tregs and prevent the development of DSA are important treatment goals for the future.
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Guido
authors.initials: G
authors.lastname: Trentadue
authors.forename: Gerard
authors.initials: G
authors.lastname: Dijkstra
mesh_terms: D064591:Allografts; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007421:Intestine, Small / Q000276:immunology*; D016377:Organ Transplantation; D013601:T-Lymphocytes / Q000276:immunology