Background. Graft survival rates after intestinal transplantation (ITx) are still the lowest in comparison to other solid organ transplants. One of the main reasons is the frequent occurrence of acute cellular rejection (ACR). Vedolizumab is an antibody against α4β7+ integrin involved in gut-homing of T cells which has been approved for inflammatory bowel diseases (IBD). We report its off-label use to treat ACR after ITx. Methods. Following abdominal wall transplantation (AWTx) and ITx, clinical course was followed biochemically. Sequential small intestinal biopsies were taken preceding, during, and after ACR treatment with vedolizumab, following the standard therapy regime for IBD. Rejection was diagnosed histologically, and proinflammatory (α4β7+, interleukin-17+) and regulatory (FoxP3+) T cells were analyzed by immunohistochemistry. Results. ACR in both the ITx and AWTx resolved upon vedolizumab treatment, which was safe, evidenced by clearing an astrovirus and primary cytomegalovirus infection. Only a slight reduction of α4β7+ cells in the mucosa was observed, and α4β7+ and regulatory T cells could still move into the lamina propria upon infection. Conclusions. Vedolizumab is a safe treatment option for ACR after ITx but its mechanism is probably not only based on inhibition of gut-selective T-cell homing.

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.

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