KIR2DS1+ decidual natural killer cells show ex-vivo activation and cytotoxicity but not cytokine secretion (MUC7P.756)
| Autor: | Angela Crespo, Tamara Tilburgs, Jack Strominger |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 192:197.8-197.8 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Decidual natural killer cells (dNK) are the most abundant lymphocytes at the fetal-maternal interface. dNK have been shown to have limited cytotoxic capacity but secrete high levels of cytokines to facilitate extravillous trophoblast (EVT) invasion. Previous studies have shown that mothers expressing the activating Killer Immunoglobulin-like Receptor-S1 (KIR2DS1) are protected from pregnancy complications when carrying a fetus expressing HLA-C2 (KIR2DS1 ligand) (Hiby et al, 2010). In this study, a significantly higher percentage of dNK expressed KIR2DS1 and KIR2DL1 than pNK. dNK and pNK expressed similar levels of perforin and granzyme B, but dNK contained markedly increased granulysin levels. Although pNK were more cytotoxic than dNK against HLA- targets, this cytotoxicity was inhibited by HLA-C1+ and HLA-C2+ targets. In contrast, the cytotoxicity of dNK from KIR2DS1+ mothers was not efficiently inhibited by HLA-C2+ targets. Moreover, higher phosphorylation of ZAP70/SYK in dNK from KIR2DS1+ mothers than KIR2DS1- mothers was showed. Thus, a higher activation state of KIR2DS1+ dNK cells interacting with HLA-C2+ targets may dominate over inhibition by HLA-C2 through KIR2DL1+ dNK. Contrary to stimulation of NK cell receptors with antibodies or cell lines, stimulation of dNK and pNK with EVT revealed no specific production of NK cytokines such as IFNγ or IL-8. These results suggest a dominant role for KIR2DS1+ dNK cells in cytotoxicity, but not cytokine secretion. |
| Databáze: | OpenAIRE |
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