PMID- 14687728 OWN - NLM STAT- MEDLINE DCOM- 20040402 LR - 20190827 IS - 0165-2478 (Print) IS - 0165-2478 (Linking) VI - 90 IP - 2-3 DP - 2003 Dec 15 TI - Lipopolysaccharide preferentially induces 4-1BB ligand expression on human monocyte-derived dendritic cells. PG - 215-21 AB - Dendritic cells (DCs) represent a promising tool for immunotherapy. A key feature in their action is to provide co-stimulatory signals for full activation of T cells. In view of recent studies demonstrating the critical role of 4-1BB co-stimulation in T cell response, it is of importance to optimize 4-1BB ligand (4-1BBL) expression on human monocyte-derived DCs (MDDCs), the DC source of many clinical studies. In this study, two types of MDDCs, generated in granulocyte-macrophage colony-stimulating factor and interleukin-4 (GM-CSF/IL-4-DCs) or in interferon-beta and IL-3 (IFN-beta/IL-3-DCs), were analyzed for 4-1BBL expression in response to several known DC activators. Immature MDDCs expressed 4-1BBLs at very low levels. Lipopolysaccharide (LPS) was the only activator that preferentially triggered 4-1BBL expression on either MDDCs, but 4-1BBL-positive cells were significantly more frequently observed on LPS-activated GM-CSF/IL-4-DCs (30.2+/-2.6% versus 14.3+/-1.2%). Combinations of multiple activating signals did not bring about enhanced 4-1BBL stimulatory capacity. In addition, plasmid DNA transfection and necrotic cell pulsing of GM-CSF/IL-4-DCs for antigen loading also resulted in 4-1BBL up-regulation. However, in all circumstances, the induced 4-1BBL levels were low in comparison with CD80 co-stimulatory molecule. Finally, by demonstrating LPS-matured GM-CSF/IL-4-DCs from sorted 4-1BBL(high) population augmented T cell expansion and survival, we propose that efforts are required to increase 4-1BBL levels on MDDCs achieved by current activation schemes. FAU - Lee, Pao-Kung AU - Lee PK AD - Department of Microbiology, Soochow University, Wai Shuang Hsi, Shih Lin, Taipei, 11102, Taiwan, ROC. FAU - Chang, Chun-Jung AU - Chang CJ FAU - Lin, Chun-Ming AU - Lin CM LA - eng PT - Journal Article PL - Netherlands TA - Immunol Lett JT - Immunology letters JID - 7910006 RN - 0 (4-1BB Ligand) RN - 0 (Lipopolysaccharides) RN - 0 (TNFSF9 protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 207137-56-2 (Interleukin-4) RN - 77238-31-4 (Interferon-beta) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - 4-1BB Ligand MH - Cell Differentiation/drug effects MH - Cell Division MH - Cells, Cultured MH - Dendritic Cells/cytology/*drug effects/immunology/*metabolism MH - Flow Cytometry MH - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - Humans MH - Interferon-beta/immunology MH - Interleukin-4/pharmacology MH - Lipopolysaccharides/*pharmacology MH - Monocytes/cytology/drug effects/metabolism MH - Time Factors MH - Tumor Necrosis Factor-alpha/*metabolism EDAT- 2003/12/23 05:00 MHDA- 2004/04/03 05:00 CRDT- 2003/12/23 05:00 PHST- 2003/12/23 05:00 [pubmed] PHST- 2004/04/03 05:00 [medline] PHST- 2003/12/23 05:00 [entrez] AID - S0165247803001962 [pii] AID - 10.1016/j.imlet.2003.08.002 [doi] PST - ppublish SO - Immunol Lett. 2003 Dec 15;90(2-3):215-21. doi: 10.1016/j.imlet.2003.08.002.