Interactions between dendritic cells and cytokine-induced killer cells lead to an activation of both populations

Dendritic cells (DCs) are major antigen-presenting cells, They are capable of capturing and processing tumor antigens, expressing lymphocyte costimula tory molecules, and secreting cytokines to initiate immune responses. Here, the authors tested the effect of cytokine-induced killer (CIK) cells, a po pulation that includes CD3(+)CD56(+) cells (natural killer T cells), with r egard to their capacity to immuno-modulate DCs. Cytokine-induced killer cel ls were cocultured with autologous DCs Generated from peripheral blood mono nuclear cells. Expression of markets typical for both populations was measu red using flow cytometry, and secretion of interleukin (IL)-12 was determin ed using enzyme-linked immunosorbent assays. Cytotoxicity assays were perfo rmed to investigate the role of IL-12 and the importance of cell-cell inter actions. Considering this, receptors for IL-12 and CD40 were blocked and co cultures were performed with cell culture inserts. Coculture of CIK cells l ed to a significant increase of DC-specific, costimulatory, and antigen-pre senting molecules in DC cultures. In addition, coculture resulted in a dram atically increase of IL-12 secretion by DCs and to a significant increase i n cytotoxic activity of CIK cells toward carcinoma cells. Blockage of IL-12 uptake decreased the cytolytic activity of CIK cells. Cytokine secretion w as shown to be important for activation of CIK cells, and also cellular int eractions between DCs and effector cells caused a higher cytolytic capacity . Interactions between DCs and CIK cells caused changes in the surface mole cule expression of both populations, led to an increase of IL-12 secretion, and rendered an improved cytotoxic activity. The natural killer T cell sub population seems to be responsible for this effect. Therefore, coculture of DCs with CIK cells may have a major impact on immunotherapeutic protocols for patients with cancer.