Cellular mechanisms underlying acute graft rejection: time for reassessment

Rejection of transplanted organs depends on an orchestrated immune response to histocompatibility antigens expressed by the grafted tissue. Effector mechanisms primarily responsible for the rejection process classically involve type 1 helper CD4+ T cells, cytotoxic CD8+ T cells and antibodies. Experimental studies revealed alternative mechanisms of rejection that implicate type 2 helper CD4+ T cells and memory CD8+ T cells as well as cells belonging to the innate immune system including natural killer cells, eosinophils and neutrophils. Furthermore, local inflammation associated with rejection is tightly regulated at the graft level by regulatory T cells and mast cells. The redundancy of rejection mechanisms explains the difficulty to induce transplantation tolerance and to develop reliable biomarkers for prediction of allograft outcome.