Mol. Hum. Reprod. Advance Access originally published online on June 9, 2009
Molecular Human Reproduction 2009 15(8):489-497; doi:10.1093/molehr/gap039
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The genotype of the NK cell receptor, KIR2DL4, influences INF
secretion by decidual natural killer cells
1 Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North Seattle, Seattle, WA 98109, Australia 2 School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA 6009, Australia 3Department of Clinical Immunology and Immunogenetics, PathWest, Royal Perth Hospital, Wellington St, Perth, WA 6847, Australia 4Department of Pathology, PathWest, King Edward Memorial/Princess Margaret Hospitals, Subiaco, WA 6008, Australia
5 Correspondence address. Tel: +61-8-9224-2899; Fax: +61-8-9224-2920; E-mail: Campbell.Witt{at}health.wa.gov.au
Natural killer (NK) cells are the predominant leukocyte in first trimester decidua and play a role in vascular remodelling through interferon gamma (IFN
) secretion. Membrane expression of the killer immunoglobulin-like receptor (KIR) KIR2DL4 on peripheral blood NK (pNK) cells is controlled by the 9A/10A transmembrane genetic polymorphism. On peripheral NK cells (pNK), KIR2DL4 can only be detected on the membrane of cells from individuals with at least one copy of the 10A allele and ligation of KIR2DL4 results in IFN secretion. In this study, we assessed KIR2DL4 expression and IFN secretion as a result of KIR2DL4 ligation, by decidual NK (dNK) cells. The 9A/10A transmembrane polymorphism was shown to control KIR2DL4 expression by dNK, as previously shown for pNK cells. Freshly isolated dNK cells from subjects with at least one 10A allele expressed KIR2DL4 whereas those from 9A homozygous subjects did not. Although freshly isolated dNK did not secrete IFN in response to KIR2DL4 ligation regardless of KIR2DL4 genotype, activation by in vitro culture with IL-2 enabled dNK cells from individuals with at least one 10A allele, but not those without a 10A allele, to secrete IFN in response to KIR2DL4 ligation. This study confirms that expression of KIR2DL4 by dNK is dependent on the 9A/10A polymorphism and that this polymorphism influences IFN secretion by dNK cells.
Key words: CD158d/cell surface molecules/cytokines/KIR2DL4/natural killer cells
These authors contributed equally to the work described in this manuscript. Submitted on January 14, 2009; resubmitted on April 22, 2009; accepted on May 29, 2009.