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Hum. Reprod. Advance Access published online on July 24, 2008
Human Reproduction, doi:10.1093/humrep/den223
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© The Author 2008. 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 online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed: the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given: if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative word this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Natural-killer cell ligands at the maternal–fetal interface: UL-16 binding proteins, MHC class-I chain related molecules, HLA-F and CD48

Richard Apps, Lucy Gardner, James Traherne, Victoria Male and Ashley Moffett1

Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK

1 Correspondence address. Tel: +44-1223-333727; Fax: +44-1223-765065; E-mail: am485{at}cam.ac.uk

BACKGROUND: In the early stages of human placentation, the decidua is invaded by fetal extravillous trophoblast (EVT) cells. Interactions between EVT cells and local decidual leukocytes are likely to contribute to immunological accommodation of the semi-allogeneic fetus.

METHODS AND RESULTS: Natural-killer group 2 member D (NKG2D) and 2B4 (CD244) are receptors ubiquitously expressed by the distinctive population of CD56 bright, uterine natural-killer cells, which dominate the decidua at the time of implantation. Here, we investigate the UL-16 binding protein (ULBP) and MHC class-I chain related molecule (MIC) ligands of NKG2D, the CD48 ligand of 2B4 and the non-classical HLA class-I molecule, HLA-F, at the maternal–fetal interface of normal pregnancies. For many of these molecules, significant mRNA expression was detected by RT-PCR in decidual and placental tissue throughout gestation. Flow cytometry of isolated cells or immunohistological staining of implantation site sections was then performed. No protein expression of NKG2D ligands or HLA-F could be detected in decidual leukocytes or fetal trophoblast cells from the first trimester. An NKG2D-Fc fusion protein identified no novel ligands for this promiscuous receptor at the maternal–fetal interface. Strong surface protein expression of CD48 by decidual leukocytes but not by trophoblast cells was detected by flow cytometry. Histological staining showed a clear aggregation of CD48+ cells around transformed spiral arteries of the implantation site.

CONCLUSIONS: We conclude that the role of NKG2D and 2B4 is not focussed on trophoblast recognition in normal pregnancy, but is more likely involved in cross-talk among maternal cells of the placental bed.

Key words: UL-16 binding protein/HLA-F/trophoblast/decidual leukocytes/natural-killer cells

Submitted on February 28, 2008; resubmitted on May 7, 2008; accepted on May 15, 2008.


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[Abstract] [Full Text] [PDF]


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