| Tolerogenicity is not an absolute property of a dendritic cell. | |
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MedLine Citation:
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PMID: 20373289 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pharmacological modulation is known to temper the immune capacity of DC, enhancing the notion that modulated Ag-bearing DC might be used therapeutically to induce tolerance. We have investigated phenotypic features shared by such DC, and queried their potential to tolerize in different settings. Immature, IL-10, TGF-beta and 1alpha,25-dihydroxyvitamin D(3)-modulated BMDC all induced tolerance to male skin in female TCR transgenic A1.RAG mice, and the modulated DC also tolerized after exposure to the TLR4-ligand LPS. Transcript profiling revealed that this was achieved despite retaining much of the normal LPS-maturation response. No shared tolerance-associated transcripts could be identified. Equivalent BMDC could not tolerize in Marilyn TCR-transgenic mice. Simultaneous presentation of both A1.RAG and Marilyn peptide-Ag (Dby-H2E(k) and Dby-H2A(b)) on immature (C57BL/6JxCBA/Ca) F1 BMDC also only achieved tolerance in A1.RAG mice. Both strains registered Ag, but Foxp3(+) Treg were only induced in A1.RAG mice. In contrast, Marilyn T cells showed greater proliferation and an inflammatory bias, in response to Ag presented by immature F1 BMDC in vitro. In summary, while pharmacological agents can skew DC to reinforce their immature tolerogenic phenotype, the outcome of presentation is ultimately an integrated response including T-cell-intrinsic components that can over-ride for immune activation. |
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Authors:
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Claire A Farquhar; Alison M Paterson; Stephen P Cobbold; Hugo Garcia Rueda; Paul J Fairchild; Stephen F Yates; Elizabeth Adams; Nigel J Saunders; Herman Waldmann; Kathleen F Nolan |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of immunology Volume: 40 ISSN: 1521-4141 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-14 Completed Date: 2010-07-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: Germany |
Other Details:
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Languages: eng Pagination: 1728-37 Citation Subset: IM |
Affiliation:
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Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigen Presentation / immunology Cell Separation Dendritic Cells / immunology* Female Flow Cytometry Immune Tolerance / immunology* Lymphocyte Activation / immunology Male Mice Mice, Inbred C57BL Mice, Transgenic Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction Receptors, Antigen, T-Cell / genetics, immunology T-Lymphocytes / immunology |
| Grant Support | |
ID/Acronym/Agency:
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G0300230l//Medical Research Council; G7904009//Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Antigen, T-Cell |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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