Fetal immune system is active, not immature

The fetal immune system is more mature in the second trimester than previously thought, which could assist research into diseases, miscarriage and immune tolerance, researchers say.

Despite being two different organisms, during gestation the mother and fetus are able to co-exist without immune responses being triggered. It had been thought that this was possible because the fetus's immune system was too immature to mount a response to material crossing over from the mother during pregnancy.

But the new study showed that the fetal immune system is present and functioning as early as 13 weeks gestation, and can operate independently from the mother. Like the adult immune system, the fetal system is able to identify foreign proteins. However, unlike the adult system the fetal immune system is much less likely to attack foreign human cells, which may explain how the fetus tolerates its mother.

The insight 'lays the foundation for future immune-directed therapies, and contributes to our knowledge of the fetal origins of certain pregnancy-associated conditions, such as pre-eclampsia,' said joint senior author Professor Jerry Chan of the KK Women’s and Children’s Hospital, Singapore. The scientists say it may also help to understand and limit gestational diabetes and miscarriage. 

The findings could also help to understand certain immune mechanisms in adults. 'Some of the events that occur during development might be important [in adult disease] and now the fetal immune system is part of this equation', said joint senior author Dr Florent Ginhoux of the Agency of Science, Technology and Research, Singapore.

Organ transplants and cell-based therapies are often unsuccessful due to immune rejection responses in patients receiving them; this research could help to find way to suppress immune responses in these situations.

Tissue was collected from fetuses between 12 and 22 weeks gestation for the study, published in Nature. The researchers identified and characterised immune cells that were present in the tissue.

They found that functional dendritic cells were present by 13 weeks of gestation. These cells act as sentinels - helping the body to determine which foreign substances should be destroyed, and recruiting other immune cells accordingly.

In the lab, these fetal dendritic cells behaved largely in the same way as adult dendritic cells. However, fetal dendritic cells suppressed immune responses to foreign human proteins, while dendritic cells from adults were more likely to mount a response to destroy them.

Professor Mike McCune of the University of California, San Francisco, who did not participate in the work told The Scientist: 'Now that we understand how tolerance works in the fetus, can we apply that to situations in the adult where tolerance might be important?'