Mechanism of NK cell activation induced by coculture with dendritic cells derived from peripheral blood monocytes

Dendritic cells (DCs) have been regarded as one of the effective antigen-pr esenting cells, but the relationship between DCs and lymphocytes, in partic ular natural killer (NK) cells, remains unclear. In this study, we evaluate d how DCs interact with both lymphocytes and NK cells using a coculture sys tem. The number of lymphocytes increased significantly when cocultured with DCs (1.8-fold increase). In particular, the proliferation of NK cells was prominent. Furthermore, the coculture of DCs with lymphocytes induced a mar ked increase in IL-12 and IFN-gamma secretion. When contact between the DCs and lymphocytes was prevented, the secretion of both IL-12 and IFN-gamma w as markedly reduced. IFN-gamma production was completely blocked by an anti -IL-12 antibody, indicating that IFN-gamma secretion was dependent on IL-12 secretion. The stimulating effect of the DCs on the proliferation of the l ymphocytes was partially suppressed by anti-IL-12 antibodies, and was compl etely attenuated when cellular contact was prevented. Furthermore, the NK c ell proliferation induced by coculture with DCs was significantly blocked b y the inhibition of the interaction of either CD40-CD40L or CD28-B7 molecul e. The coculture with DCs enhanced NK activity by 40%, and this was partial ly suppressed by anti-IL-12 antibodies and was completely blocked by the in hibition of cell-to-cell contact. These results indicate that the activatio n of NK cells by DCs is partially mediated by IL-12 secretion, and that dir ect contact between DCs and NK cells play a major role in this response.