| IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection. | |
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MedLine Citation:
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PMID: 20440075 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Persistent levels of IL-10 play a central role in progressive immune dysfunction associated with chronic viral infections such as HIV, but the underlying mechanisms are poorly understood. Because IL-10 affects the phenotypic and functional properties of DCs, which are responsible for initiating adaptive immune responses, we investigated whether IL-10 induces changes in DC phenotype and function in the context of HIV infection. Here, we show that IL-10 treatment of immature and mature human DCs in culture induced contrasting phenotypic changes in these populations: immature DCs exhibited aberrant resistance to NK cell-mediated elimination, whereas mature DCs exhibited increased susceptibility to NKG2D-dependent NK elimination. Treatment of immature and mature DCs with HIV resulted in potent IL-10 secretion and the same phenotypic and functional changes observed in the IL-10-treated cells. Consistent with these in vitro data, LNs isolated from individuals infected with HIV exhibited aberrant accumulation of a partially "immature" DC population. Together, these data suggest that the progressive immune dysfunction observed in chronic viral infections might be caused in part by IL-10-induced reversal of DC susceptibility to NK cell-mediated elimination, resulting in the accumulation of poorly immunogenic DCs in LNs, the sites of adaptive immune response induction. |
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Authors:
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Galit Alter; Daniel Kavanagh; Suzannah Rihn; Rutger Luteijn; David Brooks; Michael Oldstone; Jan van Lunzen; Marcus Altfeld |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-03 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 120 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-02 Completed Date: 2010-06-21 Revised Date: 2012-02-07 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 1905-13 Citation Subset: AIM; IM |
Affiliation:
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Ragon Institute of MGH, MIT, and Harvard, Charlestown, Massachusetts 02129, USA. galter@partners.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Differentiation
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immunology Dendritic Cells / cytology*, immunology, virology* HIV / immunology HIV Infections / immunology*, virology Humans Interleukin-10 / immunology* Killer Cells, Natural / immunology*, virology |
| Grant Support | |
ID/Acronym/Agency:
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P01 AI074415/AI/NIAID NIH HHS; R01 AI009484-41/AI/NIAID NIH HHS; R01 AI009484-42/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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130068-27-8/Interleukin-10 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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