| Dendritic cells generated in clinical grade bags strongly differ in immune functionality when compared with classical DCs generated in plates. | |
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MedLine Citation:
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PMID: 20386471 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mature dendritic cells (DCs) represent, by far, the most potent antigen-presenting cells. The development of clinical grade techniques to produce them in large numbers has rendered possible their use in clinical trials. It is therefore crucial to assess the DCs characteristics according to the methodology used to generate them, to improve the comparison and standardization of these trials. We thus compared DCs generated and matured in culture plates (pla-DCs) or in clinical grade bags (bag-DCs) by analyzing, their secretion of bioactive interleukin (IL)-12 and their capacity to induce in-vitro primary responses. We also used several molecular techniques to better characterize the functional differences between the 2 type of DCs. Mature bag-DCs displayed a mature phenotype, but did not secrete significant amounts of IL-12 and failed to initiate primary immune responses. Molecular analyses performed on immature bag-DCs showed them already engaged in a particular maturation process (early activation of nuclear factor kappa B and beta-catenin). Using microarrays, we found underexpression of receptors for the maturation cocktail in bag-DCs. In mature bag-DCs, we found crucial genes (IL-12, chemokines, and costimulatory and adhesion molecules) down-regulated. Electrophoertic mobility shift assay and Western blots showed a normal activation profile in mature pla-DCs, but not in bag-DCs where the Mek/Erk pathway was still activated. Our results strongly suggest that differentiation of monocytes into DCs in bags generates immature DCs already engaged in an inefficient type of activation, with down-regulation of genes involved in response to the maturation cocktail. This results in mature DCs unable to induce T(H)1-type responses. |
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Authors:
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Rédouane Rouas; Haidar Akl; Hussein Fayyad-Kazan; Nabil El Zein; Bassam Badran; Bérangère Nowak; Hugues Duvillier; Philippe Martiat; Philippe Lewalle |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunotherapy (Hagerstown, Md. : 1997) Volume: 33 ISSN: 1537-4513 ISO Abbreviation: J. Immunother. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-28 Completed Date: 2010-09-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9706083 Medline TA: J Immunother Country: United States |
Other Details:
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Languages: eng Pagination: 352-63 Citation Subset: IM |
Affiliation:
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Department of Hematology, Jules Bordet Institute, ULB, Brussels, Belgium. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus Antigen Presentation Antigens, Differentiation / metabolism Cancer Vaccines* Cell Culture Techniques / instrumentation, methods* Cell Differentiation Cell Nucleus / metabolism* Cells, Cultured Dendritic Cells / cytology*, immunology*, metabolism Humans Immunomagnetic Separation Immunophenotyping Interferon-gamma / secretion Lymphocyte Activation Microarray Analysis NF-kappa B / metabolism* T-Lymphocytes / immunology, metabolism, pathology |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Differentiation; 0/Cancer Vaccines; 0/NF-kappa B; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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