| CTLA-4 is expressed by human monocyte-derived dendritic cells and regulates their functions. | |
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MedLine Citation:
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PMID: 20650297 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Cytotoxic T lymphocyte antigen-4 (CTLA-4) is the major negative regulator of T-cell responses, although growing evidence supports its wider role as an immune attenuator that may also act in other cell lineages. Here, we have analyzed the expression of CTLA-4 in human monocytes and monocyte-derived dendritic cells (DCs), and the effect of its engagement on cytokine production and T-cell stimulatory activity by mature DCs. CTLA-4 was highly expressed on freshly isolated monocytes, then down-modulated upon differentiation toward immature DCs (iDCs) and it was markedly upregulated on mature DCs obtained with different stimulations (lipopolysaccharides [LPS], Poly:IC, cytokines). In line with the functional role of CTLA-4 in T cells, treatment of mDCs with an agonistic anti-CTLA-4 mAb significantly enhanced secretion of regulatory interleukin (IL)-10 but reduced secretion of IL-8/IL-12 pro-inflammatory cytokines, as well as autologous CD4+ T-cell proliferation in response to stimulation with recall antigen purified protein derivative (PPD) loaded-DCs. Neutralization of IL-10 with an anti-IL-10 antibody during the mDCs-CD4+ T-cell co-culture partially restored the ability of anti-CTLA-4-treated mDCs to stimulate T-cell proliferation in response to PPD. Taken together, our data provide the first evidence that CTLA-4 receptor is expressed by human monocyte-derived mDCs upon their full activation and that it exerts immune modulatory effects. |
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Authors:
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Stefania Laurent; Paolo Carrega; Daniele Saverino; Patrizia Piccioli; Marta Camoriano; Anna Morabito; Beatrice Dozin; Vincenzo Fontana; Rita Simone; Lorenzo Mortara; Maria Cristina Mingari; Guido Ferlazzo; Maria Pia Pistillo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-01 |
Journal Detail:
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Title: Human immunology Volume: 71 ISSN: 1879-1166 ISO Abbreviation: Hum. Immunol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8010936 Medline TA: Hum Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 934-41 Citation Subset: IM |
Copyright Information:
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2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Hematology and Oncology, University of Genoa, Genoa, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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