Document Detail


IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection.
MedLine Citation:
PMID:  20440075     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Galit Alter; Daniel Kavanagh; Suzannah Rihn; Rutger Luteijn; David Brooks; Michael Oldstone; Jan van Lunzen; Marcus Altfeld
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-05-03
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  120     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-02     Completed Date:  2010-06-21     Revised Date:  2012-02-07    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1905-13     Citation Subset:  AIM; IM    
Affiliation:
Ragon Institute of MGH, MIT, and Harvard, Charlestown, Massachusetts 02129, USA. galter@partners.org
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MeSH Terms
Descriptor/Qualifier:
Cell Differentiation / 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:
P01 AI074415/AI/NIAID NIH HHS; R01 AI009484-41/AI/NIAID NIH HHS; R01 AI009484-42/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
130068-27-8/Interleukin-10
Comments/Corrections

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