The lytic potential of human liver NK cells is restricted by their limited expression of inhibitory killer Ig-like receptors Journal Article
| Authors: | Burt, B. M.; Plitas, G.; Zhao, Z.; Bamboat, Z. M.; Nguyen, H. M.; Dupont, B.; DeMatteo, R. P. |
| Article Title: | The lytic potential of human liver NK cells is restricted by their limited expression of inhibitory killer Ig-like receptors |
| Abstract: | The human liver is enriched in NK cells which are potent effectors of the innate immune system. We have determined that liver NK cells freshly isolated from surgical specimens from patients with hepatic malignancy have less cytolytic activity than autologous blood NK cells. This difference was due to a higher proportion of CD16<sup>-</sup> NK cells in the liver and reduced cytotoxicity by CD16<sup>+</sup> liver NK cells compared with their blood counterparts. CD16<sup>+</sup> liver NK cells had similar expression of activating NK receptors and had similar intracellular granzyme B and perforin content compared with CD16<sup>+</sup> blood NK cells. CD16<sup>+</sup> liver NK cells contained a reduced fraction of cells with inhibitory killer Ig-like receptors specific for self-MHC class I (self-killer Ig-related receptor (KIR)) and an increased fraction of self-KIR<sup>neg</sup>NKG2A<sup>pos</sup> and self-KIR<sup>neg</sup>NKG2A<sup>neg</sup> cells. Using single-cell analysis of intracellular IFN-γ production and cytotoxicity assays, we determined that CD16<sup>+</sup> liver NK cells expressing self-KIR were more responsive to target cells than those cells that did not express self-KIR molecules. CD16 <sup>+</sup> liver NK cells gained cytolytic function when stimulated with IL-2 or cultured with LPS or poly(I:C)-activated autologous liver Kupffer cells. Thus, the human liver contains NK cell subsets which have reduced effector function, but under appropriate inflammatory conditions become potent killers. Copyright © 2009 by The American Association of Immunologists, Inc. |
| Keywords: | clinical article; controlled study; human tissue; comparative study; interleukin 2; cytotoxicity; cell assay; granzyme b; cd16 antigen; liver; immunology; human cell culture; gamma interferon; cell isolation; natural killer cell; killer cells, natural; killer cell immunoglobulin like receptor; lipopolysaccharide; natural killer cell receptor; natural killer cell receptor nkg2a; perforin; polyinosinic polycytidylic acid; fc receptor; cell fractionation; cytokine production; cytolysis; effector cell; inhibition kinetics; kupffer cell; liver cancer; target cell; autoimmunity; blood cell; innate immunity; blood cells; cytotoxicity, immunologic; immunity, innate; receptors, igg; receptors, kir |
| Journal Title: | Journal of Immunology |
| Volume: | 183 |
| Issue: | 3 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2009-08-01 |
| Start Page: | 1789 |
| End Page: | 1796 |
| Language: | English |
| DOI: | 10.4049/jimmunol.0900541 |
| PUBMED: | 19587011 |
| PROVIDER: | scopus |
| PMCID: | PMC3253491 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 30 November 2010" - "CODEN: JOIMA" - "Source: Scopus" |
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