Mol. Hum. Reprod. Advance Access published online on January 29, 2004
Molecular Human Reproduction, doi:10.1093/molehr/gah032
© 2004 by Oxford University Press
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1 Department of Blood Transfusion and Transplantation Immunology, University Medical Centre Nijmegen, Nijmegen, The Netherlands; Department of Blood Transfusion and Transplantation Immunology (603), University Medical Centre Nijmegen, P.O.Box 9101, Nijmegen, The Netherlands
* To whom correspondence should be addressed. E-mail: A.vandermeer{at}abti.umcn.nl.
The expression of HLA-G by invading trophoblasts suggests a role for this molecule in embryo implantation. Putative targets for HLA-G are the uterine natural killer cells (uNK) that are abundantly present at the time of implantation. Since NK cells are potent producers of a variety of cytokines, interaction with HLA-G may result in the production of cytokines involved in trophoblast differentiation or tissue remodelling. In the present study we investigated the effect of membrane-bound HLA-G (mHLA-G) on the uterine mononuclear cell population (UMC) as a whole and on uNK cells in particular by measuring proliferation and cytokine production [interferon-
Accepted December 11, 2003
Article
Membrane-bound HLA-G activates proliferation and interferon-
production by uterine natural killer cells
2 Department of Gynaecology and Obstetrics, University Medical Centre Nijmegen, Nijmegen, The Netherlands
3 Department of Pharmacology, NV Organon, 5342 CC Oss, The Netherlands
4 Department of Blood Transfusion and Transplantation Immunology, University Medical Centre Nijmegen, Nijmegen, The Netherlands
Abstract 
(IFN-)/vascular endothelial growth factor (VEGF)/leukaemia inhibitory factor (LIF)/interleukin-3 (IL-3)]. Uterine cells were isolated from endometrium of non-pregnant women at the time that the endometrium is thought to be receptive to implantation, and then co-cultured with HLA-class I-/HLA-class II+ 721.221 B-LCL cells transfected with mHLA-G. HLA-G suppressed the alloproliferative response of unfractionated UMC to 721.221 cells. Also, IFN- and IL-3 production was strongly reduced. In contrast, purified uNK cells were stimulated by mHLA-G. Proliferation as well as IFN- production was increased after co-culture with mHLA-G transfected 721.221 cells. HLA-G stimulated VEGF production by UMC as well as purified uNK cells. LIF-levels were below the detection level of our enzyme-linked immunosorbent assay. In conclusion, our data show that mHLA-G stimulates proliferation and cytokine production by NK cells, while down-modulating the response of unfractionated UMC.
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