Loading...
Please wait, while we are loading the content...
Similar Documents
Distinct indirect pathways govern human nk-cell.
| Content Provider | CiteSeerX |
|---|---|
| Author | Gorski, Kevin S. Waller, Emily L. Bjornton-Severson, Jacqueline Hanten, John A. Riter, Christie L. Kieper, William C. Gorden, Keith B. Miller, Jeffrey S. Vasilakos, John P. Tomai, Mark A. Alkan, Sefik S. |
| 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-c 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-c by purified NK cells suggesting indirect activation. IL-18 and IL-12p70 were primarily required for induction of IFN-c 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-c 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 |
| File Format | |
| Access Restriction | Open |
| Subject Keyword | Nk Cell Pathway Govern Human Nk-cell Direct Recognition Individual Role Viral Infection Tlr Agonist Polyinosinic Polycytidylic Acid Relative Induction Tlr-8 Agonist Component Purified Nk Cell Small Molecule Agonist Natural Tlr-8 Ligand Single-stranded Rna Trigger Indirect Activation Known Ligand K562 Cytolysis Nk-cell Cytotoxicity Human Nk-cell Activation Induced-self Ligand Immune Response Modifier Tlr-8 Agonist Tlr-2 To-9 High Level Toll-like Receptor Cytokine Production Ifn-c Expression Pathogen-associated Molecule |
| Content Type | Text |
