Extracellular vesicles in allograft rejection and tolerance

Extracellular vesicles (EVs), including exosomes, ectosomes and apoptotic vesicles, play an essential role in communication between cells of the innate and adaptive immune systems. Recent studies showed that EVs released after transplantation of allogeneic tissues and organs are involved in the immune recognition and response leading to rejection or tolerance in mice. After skin, pancreatic islet, and solid organ transplantation, donor-derived EVs were shown to initiate direct inflammatory alloresponses by T cells leading to acute rejection. This occurred through presentation of intact allogeneic MHC molecules on recipient antigen presenting cells (MHC cross-dressing) and subsequent activation of T cells via semi-direct allorecognition. On the other hand, some studies have documented the role of EVs in maternal tolerance of fetal alloantigens during pregnancy and immune privilege associated with spontaneous tolerance of liver allografts in laboratory rodents. The precise nature of the EVs, which are involved in rejection or tolerance, and the cells which produce them, is still unclear. Nevertheless, several reports showed that EVs released in the blood and urine by allografts can be used as biomarkers of rejection. This article reviews current knowledge on the contribution of EVs in allorecognition by T cells and discusses some mechanisms underlying their influence on T cell alloimmunity in allograft rejection or tolerance.