Document Detail


Apoptotic cells induce immunosuppression through dendritic cells: critical roles of IFN-gamma and nitric oxide.
MedLine Citation:
PMID:  18713999     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apoptotic cells induce immunosuppression through unknown mechanisms. To identify the underlying molecular mediators, we examined how apoptotic cells induce immunoregulation by dendritic cells (DC). We found that administration of DC exposed to apoptotic cells (DC(ap)) strongly inhibited the expansion of lymphocytes in draining lymph nodes in vivo and the subsequent Ag-specific activation of these lymphocytes ex vivo. Unexpectedly, DC(ap) supported T cell activation to a similar extent as normal DC in vitro, leading to proliferation and IL-2 production, except that DC(ap) did not support T cell production of IFN-gamma. Surprisingly, when DC(ap) were cocultured with normal DC, they completely lost their ability to support T cell activation, an effect reversed by anti-IFN-gamma or inhibitors of inducible NO synthase (iNOS). As expected, exposure to apoptotic cells rendered DC(ap) capable of producing much more NO in response to exogenous IFN-gamma than normal DC. Furthermore, DC(ap) from iNOS(-/-) or IFN-gammaR1(-/-) mice were not inhibitory in vitro or in vivo. Therefore, the IFN-gamma-induced production of NO by apoptotic cell-sensitized DC plays a key role in apoptotic cell-mediated immunosuppression.
Authors:
Guangwen Ren; Juanjuan Su; Xin Zhao; Liying Zhang; Jimin Zhang; Arthur I Roberts; Huatang Zhang; Gobardhan Das; Yufang Shi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  181     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-20     Completed Date:  2008-09-15     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3277-84     Citation Subset:  AIM; IM    
Affiliation:
Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / immunology*
Coculture Techniques
Dendritic Cells / immunology*
Interferon-gamma / physiology*
Lymph Nodes
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Nitric Oxide / physiology*
Nitric Oxide Synthase Type II / metabolism
T-Lymphocytes / immunology
Grant Support
ID/Acronym/Agency:
AI057596/AI/NIAID NIH HHS; AI50222/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
10102-43-9/Nitric Oxide; 82115-62-6/Interferon-gamma; EC 1.14.13.39/Nitric Oxide Synthase Type II

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