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Developmental biology - Pregnancy

Thymus Protects Mom From Dad's Genes In Fetus

A mom's thymus protects her immune response during pregnancy...

The immune system of a pregnant woman is altered during pregnancy, but not in the way previously believed. According to results from a study at Linköping University in Sweden and published in the Journal of Allergy and Clinical Immunology, the thymus, a tiny organ of the immune system located close to the heart, plays an important role during a normal pregnancy. It ensures the mother's immune system protects against infection while at the same time tolerating her unique fetus.

Researchers questioned for decades how the body manages the paradox that begins when a female becomes pregnant. On one hand, the mother's immune system must be adapted so that it does not react too strongly and reject the fetus (half of whose genes come from the father, thus making it a partially foreign object). On the other hand, the immune system must continue to provide the mother protection against infection from foreign invaders.

Researchers at Linköping University study how the immune system of a pregnant woman changes during a normal pregnancy. They have studied in particular the role played by a small organ, the thymus, in immune regulation.
The thymus plays a central role in the development of a very important group of cells in the immune system, the T cells ("T" indicates these cells are produced in the thymus). T cells determine how the immune system reacts. The body's own cells must be tolerated, while foreign objects such as bacteria and viruses must be attacked.

Despite the central role of the thymus in the immune system in general, we don't know whether its function changes during pregnancy. Most of what we currently know about the thymus comes from studies in mice. It is generally believed, based on animal studies, that the thymus becomes smaller during pregnancy with fewer T cells being released.

In animals, this decrease weakens the mother's immune defence, meaning the fetus will be tolerated. But does the same thing happen in humans? Seeking an answer, researchers investigated the output of different types of T cells in the blood of 56 pregnant and 30 non-pregnant women. They were particularly interested in one type known as regulatory T cells, as they interact with other cells of the immune system and prevent them attacking the body's own tissue.
"We have found that the output of T cells from the thymus does not change in pregnancy. We also show that the output of regulatory T cells — which can weaken the immune response — seems to increase in human pregnancy. These results may explain how the mother cannot only tolerate her fetus but also maintain her defence against infection."

Sandra Hellberg, doctoral student, Department of Clinical and Experimental Medicine, Linköping University, and one of the authors of the study.

This discovery may also be important in understanding certain autoimmune diseases, in which the body's immune system starts to attack the body's own cells. Several autoimmune diseases are connected to the function of the thymus: one example being multiple sclerosis (MS), where the brain and spinal cord are damaged by the immune system.
"Previous MS research has shown that function of the thymus is impaired by disease, and output of T cells is lower. This could explain why symptoms of women with MS often improve during pregnancy."

Jan Ernerudh, Professor and principal investigator of the study.

The research group is now planning to further investigate the function of the thymus in women with MS, and examine patients before, during and after pregnancy. This will help determine changes in the balance between different types of T cells — and if such changes contribute to symptom improvements often seen in women with MS during pregnancy.

In contrast to the rodent-based conception, the output of CD4+ T-cells is preserved, and for Treg cells even increased, during human pregnancy. This indicates a central thymic role in tolerance needed for a successful pregnancy.

Sandra Hellberg MSc, Ratnesh B. Mehta PhD, Anna Forsberg PhD, Goran Berg MD PhD, JanBrynhildsen MD PhD, OlaWinqvist MD, Maria C. Jenmalm PhD, Jan Emerudh MD PhD.

The study has been performed in collaboration with Linköping University Hospital, the maternity clinic at Vrinnevi Hospital in Norrköping and Karolinska Institutet in Stockholm. The research was financed with support from, among other sources, the Swedish Research Council and the Medical Research Council of Southeast Sweden, FORSS.

The article: "Maintained thymic output of conventional and regulatory T cells during human pregnancy", Sandra Hellberg, Ratnesh B. Mehta, Anna Forsberg, Göran Berg, Jan Brynhildsen, Ola Winqvist, Maria C. Jenmalm and Jan Ernerudh, (2018), Journal of Allergy and Clinical Immunology, published online on 9 October 2018, doi: 10.1016/j.jaci.2018.09.023

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Nov 19, 2018   Fetal Timeline   Maternal Timeline   News   News Archive

A healthy human T cell might be described as a mechanical toy: ball lands in cup - cup triggers spring - spring clamps lever onto ball — and holds tight! This new description of how a T cell works, along with its biochemistry, explains how normal T cells clamp down on dangerouly agressive T cells intent on capturing "infectors" and cancers. Credit: Nature Immunity.

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