PMID- 11759073 OWN - NLM STAT- MEDLINE DCOM- 20020514 LR - 20201219 IS - 1524-9557 (Print) IS - 1524-9557 (Linking) VI - 24 IP - 6 DP - 2001 Nov-Dec TI - Interactions between dendritic cells and cytokine-induced killer cells lead to an activation of both populations. PG - 502-10 AB - Dendritic cells (DCs) are major antigen-presenting cells. They are capable of capturing and processing tumor antigens, expressing lymphocyte costimulatory molecules, and secreting cytokines to initiate immune responses. Here, the authors tested the effect of cytokine-induced killer (CIK) cells, a population that includes CD3+CD56+ cells (natural killer T cells), with regard to their capacity to immunomodulate DCs. Cytokine-induced killer cells were cocultured with autologous DCs generated from peripheral blood mononuclear cells. Expression of markers typical for both populations was measured using flow cytometry, and secretion of interleukin (IL)-12 was determined using enzyme-linked immunosorbent assays. Cytotoxicity assays were performed to investigate the role of IL-12 and the importance of cell-cell interactions. Considering this, receptors for IL-12 and CD40 were blocked and cocultures were performed with cell culture inserts. Coculture of CIK cells led to a significant increase of DC-specific, costimulatory, and antigen-presenting molecules in DC cultures. In addition, coculture resulted in a dramatically increase of IL-12 secretion by DCs and to a significant increase in cytotoxic activity of CIK cells toward carcinoma cells. Blockage of IL-12 uptake decreased the cytolytic activity of CIK cells. Cytokine secretion was shown to be important for activation of CIK cells, and also cellular interactions between DCs and effector cells caused a higher cytolytic capacity. Interactions between DCs and CIK cells caused changes in the surface molecule expression of both populations, led to an increase of IL-12 secretion, and rendered an improved cytotoxic activity. The natural killer T cell subpopulation 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. FAU - Marten, A AU - Marten A AD - Medizinische Klinik und Poliklinik I, Allgemeine Innere Medizin, Rheinische Friedrich-Wilhelms-Universitat, Bonn, Germany. FAU - Ziske, C AU - Ziske C FAU - Schottker, B AU - Schottker B FAU - Renoth, S AU - Renoth S FAU - Weineck, S AU - Weineck S FAU - Buttgereit, P AU - Buttgereit P FAU - Schakowski, F AU - Schakowski F FAU - von Rucker, A AU - von Rucker A FAU - Sauerbruch, T AU - Sauerbruch T FAU - Schmidt-Wolf, I G AU - Schmidt-Wolf IG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunother JT - Journal of immunotherapy (Hagerstown, Md. : 1997) JID - 9706083 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Receptors, Interleukin) RN - 0 (Receptors, Interleukin-12) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Biomarkers MH - Cell Communication/immunology MH - Cell Membrane/immunology MH - Cells, Cultured MH - Coculture Techniques MH - Cytokines/*immunology MH - Cytotoxicity, Immunologic MH - Dendritic Cells/*immunology MH - Humans MH - Immunophenotyping MH - Interleukin-12/metabolism MH - Killer Cells, Natural/*immunology MH - Lymphocyte Activation/*immunology MH - Receptors, Interleukin/immunology MH - Receptors, Interleukin-12 MH - Tumor Cells, Cultured EDAT- 2002/01/05 10:00 MHDA- 2002/05/15 10:01 CRDT- 2002/01/05 10:00 PHST- 2002/01/05 10:00 [pubmed] PHST- 2002/05/15 10:01 [medline] PHST- 2002/01/05 10:00 [entrez] AID - 10.1097/00002371-200111000-00007 [doi] PST - ppublish SO - J Immunother. 2001 Nov-Dec;24(6):502-10. doi: 10.1097/00002371-200111000-00007.