DCs stimulated the growth and differentiation of CD4 New York, New York 10021 and CD8 alloreactive T cells, while, in the “efferent” phase, the activated T cells responded to other types of antigen-presenting cells (APC) in an allogeneic MHC-Introduction specific manner. The same two stages in cell-mediated Transplantation research has provided many insights immunity were also observed in responses to nominal into fundamental aspects of immunology, including the antigens, particularly in the induction of the primary antibiology of dendritic cells (DCs). The critical tools of body response (reviewed in Steinman, 1991). transplantation research—antibodies to major histo- Strong staining for MHC class II and an absence of compatibility complex (MHC) class I and II products, the B cell or macrophage markers were used to search for mixed leukocyte reaction (MLR), and rodent experimen- DCs in situ. In tissue sections from rats and humans, tal models of skin and organ transplantation—were vital MHC class II–positive DCs were identified in the interstito the initial characterization of DCs as distinct leuko- tial spaces of all organs examined except the brain pacytes, specialized to initiate graft rejection (reviewed in renchyma. In lymphoid tissues, DCs are abundant in the Steinman, 1991). It was proposed that bone marrow– T cell areas of spleen and lymph nodes and the medulla derived DCs in the allograft were the foes responsible of the thymus. The same criteria were used to identify DCs in human blood and in afferent lymph from many for immunogenicity. An oversimplified concept arose species, but DCs were absent in efferent lymph. When that DC elimination, something that is very difficult to isolated DCs were reinfused into rodents, the DCs miachieve, would lead to graft acceptance. In fact, the grated to the T cell areas of the draining lymphoid organ. situation is far more complicated. DCs in both the graft After antigen administration by intramuscular or intravedonor and the recipient can act as the foe, stimulating nous routes, the DCs in the lymph and spleen were the rejection by what are termed the direct and indirect main cell type able to present antigen to T cells. The pathways, respectively. However, there is also emerging concept arose that DCs could pick up antigens in the evidence that DCs can act as a friend, promoting graft periphery and migrate to the T cell areas (in spleen via acceptance. More broadly, the studies of DCs in transthe blood, in lymph nodes via the lymph), where they plantation are valuable for understanding their role in could either initiate an immune response to the antigens immunity to other antigens and, recently, in peripheral that the DCs were presenting or simply die (Figure 1). tolerance. This review addresses some potential roles of As we will consider below, death is followed by re-pre-