Gene modification helps mouse mum tolerate fetus

Immune rejection, the body's defence
mechanism, triggered in response to foreign tissues, is a huge problem for
transplant operations. But why does a mother's immune system not reject the
developing fetus?

The answer may lie in modifications to
genes that usually activate part of the immune response, according to
scientists.

A group of proteins called chemokines
usually trigger the destruction of foreign tissues, but in this study,
published in Science, researchers discovered that in mice they appear to be
turned off during pregnancy.

'This is a very exciting finding for
us because it gives a satisfying explanation for why the fetus isn't rejected
during pregnancy, which is a fundamental question for the medical community
with clear implications for human pregnancy', lead researcher Dr Adrian Erlebacher
said.

Normally, these chemokines
recruit immune cells, called T cells, to the foreign tissue, which destroy it. Dr
Erlebacher explained that in during pregnancy this doesn't happen - the
specialised membrane in the uterus that surrounds the embryo and placenta, the decidua,
is instead a 'zone of relative immunological inactivity'.

They found that the implantation
of an embryo causes alterations to the genes that produce the chemokine proteins in decidua
cells, in a process called epigenetic silencing. This means that they do not
function in the same way, and so do not signal for T cells to attack the
developing fetus.

The team, from the New York School of
Medicine, is now investigating whether the same mechanisms apply to human pregnancy,
and if failures in the process could account for complications such as preterm
labour, spontaneous abortion and pre-eclampsia.

It is hoped these findings will also
be of use in other fields where immune-tolerance is an important issue,
including organ transplantation and autoimmune diseases.