Antibody-mediated rejection: emergence of animal models to answer clinical questions

Decades of experiments in small animals had tipped the balance of opinion away from antibodies as a cause of transplant rejection. However, clinical experience, especially with sensitized patients, has convinced basic immunologists of the need to develop models to investigate mechanisms underlying antibody-mediated rejection (AMR). This resurgent interest has resulted in several new rodent models to investigate antibody-mediated mechanisms of heart and renal allograft injury, but satisfactory models of chronic AMR remain more elusive. Nevertheless, these new studies have begun to reveal many insights into the molecular and pathological sequelae of antibody binding to the allograft endothelium. In addition, complement-independent and complement-dependent effects of antibodies on endothelial cells have been identified in vitro. As small animal models become better defined, it is anticipated that they will be more widely used to answer further questions concerning mechanisms of antibody-mediated tissue injury as well as to design therapeutic interventions.