Our adoptive transfer studies showed that CD8 + T cells are responsible for induction of long-lasting tolerance toward donor alloantigen. We therefore proposed that Flt3L-mobilized recipient DCs might process indirect antigen presentation of allopeptides to induce tolerance for host CD8 + alloreactive T cells, which are the main effector mechanism of cellular rejection across an MHC class I barrier. This notion is well supported by a recent study, in which Rapa-conditioned, alloAg-pulsed DC can present acquired MHCpeptide complexes from donor cells and modulate directly-reactive CD8 + T cell function, and through which, these DCs enhance Agspecific CD8 + T cell undergoing apoptosis [42] . Furthermore, CD8 + CD28 -T cells may also play an important role in tolerance induction. These T cells represent a transient state of effector CD8 + T cells, which promotes the production of the immunosuppressive cytokine IL-10 [43, 44] . Emerging data suggest that the appearance of these T cells in transplant recipients is associated with better graft acceptance along with stable function [45, 46, 47] . Finally, our data indicate that autophagy plays an important role in the protective effect of Flt3L in combination with Rapa on cardiac allograft survival. The possible mechanisms is that autophagy delivers self-proteins for MHC class II loading, and their peptidic fragments are essential for the deletion of selfreactive T cells in the thymus. Recent studies have also suggested that the possible link between autophagy and tolerance is that autophagy plays a role in the removal of apoptotic cell corpses [48] . Regarding to the effect of autophagy on allograft survival seems controversial. In a rat liver transplantation study, it has been shown that autophagy-associated hepatocyte death triggers liver graft dysfunction, and suppression of autophagy prevent cold ischemia-warm reperfusion injury associated with liver transplantation [49] . Thus, further relevant investigations are needed.