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Mol. Hum. Reprod. Advance Access published online on June 9, 2009

Molecular Human Reproduction, doi:10.1093/molehr/gap039
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The genotype of the NK cell receptor, KIR2DL4, influences INF{gamma} secretion by decidual natural killer cells

J.P. Goodridge4,*, L.J. Lathbury1,*, E. John2, A.K. Charles3, F.T. Christiansen1,2 and C.S. Witt2

1School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, 6009, Western Australia 2Dept of Clinical Immunology and Immunogenetics, PathWest, Royal Perth Hospital, Wellington St, Perth, 6847, Western Australia 3Department of Pathology, PathWest, King Edward Memorial/Princess Margaret Hospitals, Subiaco, 6008, Western Australia 4Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North Seattle, WA 98109

CORRESPONDING AUTHOR: Dr Campbell WITT Dept Clinical Immunology and Immunogenetics, PathWest, Royal Perth Hospital, Wellington St, Perth, Western Australia, 6847. Ph: 61-8-9224 2899, Fax: 61-8-9224 2920, Email: 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{gamma}) 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{gamma} secretion. In this study, we assessed KIR2DL4 expression and IFN{gamma} secretion as a result of KIR2DL4 ligation, by decidual NK cells (dNK). 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 whilst those from 9A homozygous subjects did not. Although freshly isolated dNK did not secrete IFN{gamma} 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{gamma} 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{gamma} 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 April 14, 2009; resubmitted on May 24, 2009; accepted on May 29, 2009.


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