Pregnancy: Ceasefire in the Decidua

17. August 2012

When it comes to foreign tissue, the immune system does not exactly act lightly. This makes it all the more astounding that a foetus in the womb does not fall victim to the immune system. U.S. scientists can now perhaps explain the paradox.

The human immune system is quite strict when deciding what is not and what is foreign to the body. Help is obtained from antigens. Presented by the major histocompatibility complex (MHC) on the surface of cells, they show the immune system from where the tissue originates. Lymphocytes continually check the adhering appendages for their status as part of the body itself. Everything that they do not recognise is vigorously fought in order to protect individuals from attack. Immune cell-activated T-cells are summoned to the place of battle. Having arrived, the immune cells attack the foreign tissue.

Expectant mothers have a problem here. The genome of the foetus which they carry around in the belly is half from the mother and the other half from the father. The logical consequence would be that the paternal antigens activate the immune system. This foreign tissue would be removed ever so quickly. The billions of people on this earth however defy this. Against all laws of transplantation medicine, the genetically foreign child is tolerated for nine months by the mother’s immune system. For decades, researchers have been trying to resolve this paradox.

Perhaps the immune system of the mother is weakened during pregnancy, some scientists suspected. Yet when they compared the immune status of pregnant and non-pregnant women, there was no difference. The immune system is not weakened in general. Other toxins or intruders are rigorously destroyed. It also has nothing to do with the nature of foetal cells in themselves, because in other circumstances these can very well trigger an immune response.

There must be some sort of protective barrier that prevents the immune cells from penetrating the growing child, believes Ardrian Erlebacher, pathologist at the University Cancer Institute of New York. Already some time ago he made a search and found out that T-cells for some reason do not fulfill their defensive duties properly against the growing child. So he together with his colleagues then took on the decidua, the reconstructed part of the endometrium which surrounds the foetus and placenta. “What we found was in every aspect unexpected”, says Erlebacher, the results of which he has published in the journal Science.

The scientists discovered that with the implantation of an embryo a process is initiated that switches off the immune system. So that the immune system can attack an intruder, it requires a signal. It is precisely that which is stopped during the development of the child. In pregnant mice, the scientists could see that the genetic information for these signaling molecules, the chemokines, were packed in the nucleus differently. Thus they cannot be read. The consequence: no T-cells accumulate in the decidua. An attack on the foetus and placenta is excluded. “The decidua becomes a zone of immunological inactivity”, says Erlebacher.

The altered packaging does not have effects on the genetic information itself. There is no mutation, there are no breaks in the genetic information. The alterations which the researchers have found, are epigenetic. How does it work? Histones are the “packaging” of DNA. The DNA is wrapped around these proteins, as if around a chain of pearls, linear wise. In order to read genes, the chain is loosened up repeatedly. Changes to the histones can also lead to the situation that they are packed so tightly that a near approach is no longer possible. It also seems to be so in this case.

The results not only provide important clues for understanding a normal pregnancy. Error in this procedure according to the researchers could lead to premature birth, miscarriage or late pregnancy poisoning. Erlebacher and his colleagues are now investigating whether these same alterations in actuality lead to the protection of the unborn child from the defence system of the mother in humans.

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