The road to transplant tolerance is paved with good dendritic cells

After transplantation, recipient T cells can recognize donor antigens either by interacting with MHC class II on donor bone marrow‐derived cells (direct allorecognition), or by recognizing allogeneic peptides bound to self‐MHC class II molecules on recipient antigen presenting cells (indirect allorecognition). The activation of pro‐inflammatory T cells via either of these pathways leads to allograft rejection, so the suppression of both of these pathways is needed to achieve transplantation tolerance. A study in this issue of the European Journal of Immunology Eur. J. Immunol. 2013. 43: 734–746] shows that allogeneic dendritic cells (DCs) modified to either lack expression of CD80/86 or over‐express indoleamine 2,3‐dioxygenase (IDO) are able to inhibit direct and/or indirect alloresponses in vitro and in vivo in mice. Notably, both allorecognition pathways were suppressed by the coexpression of self‐ and allo‐MHC molecules on semi‐allogeneic DCs. This Commentary discusses the challenges and potential of using genetically‐modified DCs to suppress alloreactivity in the context of transplant tolerance.