PMID- 15476255 OWN - NLM STAT- MEDLINE DCOM- 20041130 LR - 20061115 IS - 0004-3591 (Print) IS - 0004-3591 (Linking) VI - 50 IP - 10 DP - 2004 Oct TI - Antigen-specific immunomodulation of collagen-induced arthritis with tumor necrosis factor-stimulated dendritic cells. PG - 3354-64 AB - OBJECTIVE: Dendritic cells (DCs) are crucial for the initiation of T cell immunity and therefore play an important role in the initiation and regulation of immune responses in arthritis. Full mobilization of effector T cells depends on the proper maturation of DCs. Current evidence indicates that the type of T cell response induced is crucially dependent on the activation status of the DCs. In this study, we explored the immunologic effects of differentially matured DCs on the development of collagen-induced arthritis (CIA). METHODS: Bone marrow-derived DCs were cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Before immunization with bovine type II collagen (CII) protein, mice were repeatedly injected with DCs that had been pulsed with CII. Immature, semimature, or fully mature DCs were injected. Mice were boosted on day 21 after CII immunization, and the disease course was monitored. RESULTS: While vaccination with immature or lipopolysaccharide-activated DCs had no significant effect on the disease course, administration of antigen-loaded, tumor necrosis factor (TNF)-modulated DCs propagated in GM-CSF with or without interleukin-4 resulted in a delayed onset of arthritis and a lower clinical score. The response was antigen-specific, since TNF-treated DCs pulsed with a control antigen did not modify the disease course. A specific decrease in the collagen-specific "Th1-associated" IgG2a response was observed, whereas IgG1 titers were unaffected. CONCLUSION: CIA can be prevented through vaccination with TNF-matured DCs in an antigen-specific manner. These findings provide a rationale for immunotherapy using DCs in rheumatoid arthritis. CI - Copyright 2004 American College of Rheumatology FAU - van Duivenvoorde, Leonie M AU - van Duivenvoorde LM AD - Leiden University Medical Centre, Leiden, The Netherlands. FAU - Louis-Plence, Pascale AU - Louis-Plence P FAU - Apparailly, Florence AU - Apparailly F FAU - van der Voort, Ellen I H AU - van der Voort EI FAU - Huizinga, Tom W J AU - Huizinga TW FAU - Jorgensen, Christian AU - Jorgensen C FAU - Toes, Rene E M AU - Toes RE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Tumor Necrosis Factor-alpha) RN - 207137-56-2 (Interleukin-4) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Arthritis, Experimental/chemically induced/*immunology/prevention & control MH - Cells, Cultured MH - Collagen MH - Dendritic Cells/*immunology MH - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - Immunization MH - Interleukin-4/pharmacology MH - Mice MH - Mice, Inbred DBA MH - T-Lymphocytes, Regulatory/immunology MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 2004/10/12 09:00 MHDA- 2004/12/16 09:00 CRDT- 2004/10/12 09:00 PHST- 2004/10/12 09:00 [pubmed] PHST- 2004/12/16 09:00 [medline] PHST- 2004/10/12 09:00 [entrez] AID - 10.1002/art.20513 [doi] PST - ppublish SO - Arthritis Rheum. 2004 Oct;50(10):3354-64. doi: 10.1002/art.20513.