Dendritic cells as promoters of transplant tolerance

Abstract

Dendritic cells (DCs) play a crucial role during the initiation of immune responses against non-self antigens. Following organ transplantation, activated donor- and recipient-derived DCs participate actively in graft rejection by sensitising recipient T cells via the direct or indirect pathways of allorecognition, respectively. There is increasing evidence that immature/semi-mature DCs induce antigen-specific unresponsiveness or tolerance to self antigens, both in central lymphoid tissue and in the periphery, through a variety of mechanisms (deletion, anergy and regulation). In the past few years, DC-based therapy of experimental allograft rejection has focused on ex vivo biological, pharmacological and genetic engineering of DCs to mimic/enhance their natural tolerogenicity. Successful outcomes in rodent models have built the case that DC-based therapy may provide a novel approach to transplant tolerance. Ongoing research into the role that DCs play in the induction of tolerance should allow for its clinical application in the near future.