Dendritic cells acquire antigens from live cells for cross-presentation toCTL

Dendritic cells (DC) can readily capture Ag from dead and dying cells for p resentation to MHC class I-restricted CTL, We now show by using a primate m odel that DC also acquire Ag from healthy cells, including other DC, Cocult ure assays showed that fluorescently labeled plasma membrane was rapidly an d efficiently transferred between DC, and transfer of intracellular protein s was observed to a lesser extent. Acquisition of labeled plasma membrane a nd intracellular protein was cell contact-dependent and was primarily a fun ction of immature DC, whereas both immature and CD40L-matured DC could serv e as donors. Moreover, immature DC could acquire labeled plasma membrane an d intracellular proteins from a wide range of hemopoietic cells, including macrophages, B cells, and activated T cells. Notably, macrophages, which re adily phagocytose apoptotic bodies, were very inefficient at acquiring labe led plasma membrane and intracellular proteins from other live macrophages or DC. With live-cell imaging techniques, we demonstrate that individual DC physically extract plasma membrane from other DC, generating endocytic ves icles of up to 1 mum in diameter. Finally, DC but not macrophages acquired an endogenous melanoma Ag expressed by live DC and cross-presented Ag to MH C class I-restricted CTL, demonstrating the immunological relevance of our finding, These data show for the first time that DC readily acquire Ag from other live cells. We suggest that Ag acquisition from live cells may provi de a novel mechanism whereby DC can present Ag in the absence of direct inf ection, and may serve to expand and regulate the immune response in vivo.