‘Natural Killer’ immune cells reveal factors for reproductive success

3rd November 2008

Immune cells known as natural killer (NK) cells are linked with pregnancy problems including pre-eclampsia and recurrent miscarriage. Collaborative research between scientists at the Babraham Institute and Centre for Trophoblast Research in Cambridge is illuminating the role that pregnancy-related NK cells play in moderating the biochemical interactions at the boundary between maternal tissues and the developing foetus. Their findings, reported in November’s Journal of Immunology, reveal that uterine NK cells are ‘armed’ with specific receptors, enabling interaction with other molecules to ensure that the placenta develops normally and the pregnancy is successful.

Natural Killer (NK) cells, a type of white blood cell, defend us from tumours, viruses and other potential dangers. They sense their environment through a repertoire of surface proteins (receptors), which detect other immune molecules, those belonging to the Major Histocompatability Complex (MHC). This allows NK cells to distinguish ‘friend from foe’ and attack cells that have either lost self-MHC molecules or express a different set of MHC molecules.

A specialised set of NK cells accumulates in the uterus during each menstrual cycle and, if a fertilised embryo implants, their numbers rapidly swell at the maternal-foetal boundary. The role of these cells in pregnancy is enigmatic. Instead of the killing function normally associated with NK cells, in the uterus NK cells work in a different way; they are thought to make factors known as cytokines, which help to modify the maternal arteries supplying the developing foetus with the necessary blood, nutrients and oxygen. These dramatic tissue changes must be orchestrated in the context of the genetic diversity between the maternal immune cells and the paternal genes expressed on the developing placenta. Hostile interactions between maternal uterine NK cells and paternal MHC molecules are associated with an increased likelihood of abnormal pregnancies and recurrent miscarriage. However, the receptors enabling uterine NK cells to interact with MHC are only recently being uncovered. It is also unclear how maternal immune cells recognise paternal molecules in the unique micro-environment of the developing placenta, preventing an attack being mounted.

The Cambridge collaborators have identified the repertoire of activating and inhibitory receptors present on uterine NK cells and demonstrated that they are different from blood NK cells in terms of their adhesion, activation and MHC recognition capabilities.

 “Not enough is known about these unique cells and their important role in pregnancy,” said Hakim Yadi, lead author and PhD student at the Babraham Institute. “This unprecedented and in-depth analysis of uterine killer cells is the necessary groundwork upon which we can build new knowledge. This will aid us in determining the factors that regulate reproductive success”.

The team’s analysis also revealed that uterine NK cells can be separated in two previously unappreciated subsets, opening up new questions related to their origin and functions, insights that will further understanding of the unique role of immune cells at the maternal-foetal interface.

This research was supported by the BBSRC, through a Babraham Institute Synergy Award to Drs. Francesco Colucci and Myriam Hemberger, an MRC Project Grant to Francesco Colucci and by the recently established Centre for Trophoblast Research at the University of Cambridge.

Contact details:

Dr Claire Cockcroft   
Head, External Relations
The Babraham Institute
Babraham Research Campus
Cambridge   CB22 3AT
United Kingdom

Email:   claire.cockcroft@babraham.ac.uk
Tel:   +44 (0)1223 496260
Fax:   +44 (0)1223 496002

Notes to Editors:

The Babraham Institute is a charitable organisation devoted to biomedical research and is an institute of the Biotechnology and Biological Sciences Research Council (BBSRC). The Institute’s research is focused on understanding the biological events that underlie the normal functions of cells and on how their failure or abnormality may lead to disease. As such, Institute scientists are striving to find cures for conditions where there is currently no treatment or where the existing treatment is not fully effective or causes serious side effects. The latest technologies are being used to study the basis of conditions such as neurodegenerative disorders, birth defects, cancer and diseases of the immune and cardiovascular systems. With a strategic focus on ‘healthy ageing’, novel approaches for tackling chronic diseases and public health concerns like obesity are being discovered. The Institute’s innovative research is commercialised through Babraham Bioscience Technologies (BBT) Ltd, which also manages Babraham’s vibrant Bioincubator on the Babraham Research Campus, six miles south-east of Cambridge.  Website: www.babraham.ac.uk

The Centre for Trophoblast Research is an exciting new inter-departmental initiative that aims to promote the study of placental biology, with special reference to the trophoblast, both within and outside Cambridge. The centre, which draws together researchers from Babraham, The Department of Physiology, Development and Neuroscience, The Gurdon Institute and Addenbrookes Hospital, was officially launched in July 2008 and aims to facilitate interactions and collaborations between established researchers, both nationally and internationally. The Centre aims to promote research and teaching in placental biology and the developmental origins of the trophoblast within the University of Cambridge and affiliated institutes through Next Generation Research Fellowships, Graduate Studentships, seminars, workshops, and infrastructural support. One of the Centre’s principal aims, however, is to encourage young investigators into the field and foster their careers.  http://www.trophoblast.cam.ac.uk/