Abstract:
:NK cells limit the emergence of cancers and viral infections by surveillance of 'missing-self' and 'induced-self' ligands, and by direct recognition of pathogen-associated molecules. We examined individual roles for Toll-like receptors (TLRs)-7 and -8 in human NK-cell activation using synthetic, small molecule agonists of either TLR-7 (imiquimod and 3M-001), TLR-8 (3M-002) or both TLR-7/8 (3M-003 and R-848) for comparison with known ligands of TLR-2 to -9. Tracking cytokine production in PBMC initially revealed that a subset of TLR agonists including polyinosinic-polycytidylic acid (poly I:C), 3M-002, 3M-003, R-848 and single-stranded RNA trigger relatively high levels of IFN-gamma expression by NK cells. Isolated NK cells did not express TLR-7 or TLR-8. Unlike MALP-2 and poly I:C, 3M-001-3 did not induce expression of either CD69 or IFN-gamma by purified NK cells suggesting indirect activation. IL-18 and IL-12p70 were primarily required for induction of IFN-gamma by both synthetic and natural TLR-8 ligands, while type I IFN was required for induction of CD69 on NK cells by the TLR-7 agonist 3M-001. In addition to expression of IFN-gamma and CD69, relative induction of NK-cell cytotoxicity by TLR-7 and TLR-8 agonists was compared. Immune response modifiers (IRMs) with a TLR-8 agonist component (3M-002 and 3M-003) stimulated greater levels of K562 cytolysis than achieved with 3M-001 or IL-2 (1000 units ml(-1)). In vivo NK-cell cytotoxicity was also enhanced by R-848, but not in type I IFNR-deficient mice. We conclude that IRMs can modulate NK-cell function both in vitro and in vivo and that distinct indirect pathways control human NK-cell activation by TLR-7 and TLR-8 agonists.
journal_name
Int Immunoljournal_title
International immunologyauthors
Gorski KS,Waller EL,Bjornton-Severson J,Hanten JA,Riter CL,Kieper WC,Gorden KB,Miller JS,Vasilakos JP,Tomai MA,Alkan SSdoi
10.1093/intimm/dxl046subject
Has Abstractpub_date
2006-07-01 00:00:00pages
1115-26issue
7eissn
0953-8178issn
1460-2377pii
dxl046journal_volume
18pub_type
杂志文章abstract::Dendritic cells (DCs) are responsible for the initiation of immune responses. Our study demonstrates a new pathway for generating a large quantity of stimulatory monocyte-derived DCs (Mo-DCs) from human monocytes using anti-4-1BB ligand (4-1BBL) mAb to trigger reverse signaling. The anti-4-1BBL-driven Mo-DCs (DCs(alph...
journal_title:International immunology
pub_type: 杂志文章
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journal_title:International immunology
pub_type: 杂志文章
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更新日期:1998-10-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
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更新日期:1994-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:1995-04-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
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更新日期:2014-05-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh399
更新日期:2006-04-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
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更新日期:2007-04-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.8.1049
更新日期:1998-08-01 00:00:00
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journal_title:International immunology
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doi:10.1093/intimm/dxm086
更新日期:2007-10-01 00:00:00
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journal_title:International immunology
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doi:10.1093/intimm/dxn009
更新日期:2008-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/intimm/13.9.1099
更新日期:2001-09-01 00:00:00
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更新日期:1993-02-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
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更新日期:2004-10-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章,评审
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更新日期:2020-06-26 00:00:00
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journal_title:International immunology
pub_type: 临床试验,杂志文章
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journal_title:International immunology
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journal_title:International immunology
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更新日期:2016-02-01 00:00:00
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journal_title:International immunology
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journal_title:International immunology
pub_type: 杂志文章
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journal_title:International immunology
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