Dendritic cells and macrophages have been attributed with stimulatory capacity for in vivo and in vitro immune responses. However, the relative contribution of each of these cell types has long been in dispute. Therefore, the differential ability of dendritic cells and macrophages (splenic adherent cells [SACs]) to stimulate pancreatic islet allograft rejection in reversed alloxan-induced diabetic rats was examined. Rats bearing established allografts were challenged with various dosages of donor-strain dendritic cells or SACs, and graft rejection was assessed by analysis of plasma glucose levels and/or histological criteria. Marked differences in the ability to stimulate allograft rejection were observed at the 10(5)-cell dosage; 10(5) dendritic cells induced graft rejection in five of six rats (1 rat required 2 injections), whereas 10(5) SACs failed to induce rejection in four of four rats (P less than 0.10, chi 2 test). Challenge stimuli consisting of less than or equal to 10(5) SACs or less than or equal to 10(4) dendritic cells failed to induce graft rejection. These findings indicate that dendritic cells are potent stimulator cells for in vivo immune responses. Previous studies indicated that as few as 10(3) dendritic cells initiate allograft rejection in nondiabetic recipients. That more dendritic cells were required to stimulate rejection in reversed diabetic recipients compared with nondiabetic recipients suggests that other factors, such as the diabetic state and the production of a tolerant status achieved by larger amounts of grafted tissue, may influence graft survival.
Dendritic cells (DCs) are potent antigen-presenting cells for a variety of immune responses; however, their mechanism of action has not been established. It is known that DCs can cluster with one another and with other cell types during in vitro immune responses, and clustering may be essential for the activation of resting lymphocytes. In this study, ultrastructural examination of clusters that form during extended culture of enriched rat splenic DCs (approximately 70% DCs) is reported. DCs were readily distinguished from other cell types, which included lymphocytes and macrophages. DCs displayed characteristic veils and/or dendritic processes that intertwined with processes of other cells within the cluster, or extended from the cluster periphery. Occasional DCs contained large vacuoles lined with small vesicles. A paramount feature of DCs is their constitutive expression of high levels of surface major histocompatibility complex class II antigens. The surface distribution of class II antigens on clustering DCs was examined using 10 nm immunogold labeling techniques and high-resolution scanning electron microscopy. DCs were readily distinguished by morphologic criteria, and examination of various surface membrane regions revealed a differential distribution of class II antigens. Gold label was frequently distributed in linear arrays and clusters, suggesting a cytoskeletal role in the recycling/redistribution of Class II antigens. These morphologic findings further an understanding of basic DC biology and their mechanism of action as antigen-presenting cells.
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