Comparative Analysis of Potency of Splenic Dendritic and Adherent Cells (Macrophages) as Alloantigen Presenters In Vivo

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 10⁵-cell dosage; 10⁵ dendritic cells induced graft rejection in five of six rats (1 rat required 2 injections), whereas 10⁵ SACs failed to induce rejection in four of four rats (P < 0.10, χ² test). Challenge stimuli consisting of ≤ 10⁵ SACs or ≤10⁴ 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 10³ 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.