The Lytic Potential of Human Liver NK Cells Is Restricted by Their Limited Expression of Inhibitory Killer Ig-Like Receptors
- 1 August 2009
- journal article
- research article
- Published by The American Association of Immunologists
- Vol. 183 (3), 1789-1796
- https://doi.org/10.4049/jimmunol.0900541
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− NK cells in the liver and reduced cytotoxicity by CD16+ liver NK cells compared with their blood counterparts. CD16+ liver NK cells had similar expression of activating NK receptors and had similar intracellular granzyme B and perforin content compared with CD16+ blood NK cells. CD16+ 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-KIRnegNKG2Apos and self-KIRnegNKG2Aneg cells. Using single-cell analysis of intracellular IFN-γ production and cytotoxicity assays, we determined that CD16+ liver NK cells expressing self-KIR were more responsive to target cells than those cells that did not express self-KIR molecules. CD16+ 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.Keywords
This publication has 51 references indexed in Scilit:
- Human Liver Dendritic Cells Promote T Cell HyporesponsivenessPublished by The American Association of Immunologists ,2009
- Human natural killer cellsBlood, 2008
- Up on the tightrope: natural killer cell activation and inhibitionNature Immunology, 2008
- HLA alleles determine differences in human natural killer cell responsiveness and potencyProceedings of the National Academy of Sciences of the United States of America, 2008
- Tonsilar NK Cells Restrict B Cell Transformation by the Epstein-Barr Virus via IFN-γPLoS Pathogens, 2008
- TLR-dependent cross talk between human Kupffer cells and NK cellsThe Journal of Experimental Medicine, 2008
- A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immatureBlood, 2007
- The activation state of human intrahepatic lymphocytesClinical and Experimental Immunology, 2007
- Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell–mediated liver damageThe Journal of Experimental Medicine, 2007
- Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cellsNature, 2006