Preterm labour, a common pregnancy complication, may sometimes happen when the foetal immune system "wakes up" too early and begins to reject the mother, causing the uterus to contract, a study has found.
An initial infection in the mother can result in inflammation and arouse the foetal immune system.
The foetal immune cells confuse the mother's cells for an invader and mount an attack, in the form of inflammatory chemicals.
These chemicals then trigger contractions, leading to preterm labour, the leading cause of infant mortality.
"The dogma has always been that the foetus has a very immature immune system, and as a result, people haven't really considered its possible role in pregnancy complications," said Tippi MacKenzie, an associate professor in the UCSF.
"We showed that in patients who have preterm labour as a result of some kind of infection or inflammation - the most common cause of preterm labour - the foetal immune system awakens prematurely and may trigger labour," said MacKenzie.
In the study published in the journal Science Translational Medicine, researchers tested umbilical cord blood, which contains foetal cells, along with blood taken from 89 women who had healthy pregnancies and 70 who went into early labour.
However, the scientists saw no signs of an immune response in the mother's blood. Instead, they detected activation in two types of immune cells in the cord blood of preterm infants.
The researchers also found greater numbers of the mother's cells circulating in the cord blood of preterm infants.
During pregnancy, cells from the mother and the foetus travel back and forth across the placenta. Just as in an organ transplant, the immune systems of the mother and the foetus have to tolerate one another, so the foetus is not rejected.
This tolerance is governed by immune cells known as regulatory T cells, which dampen the immune system by keeping the other types of T cells in check.
However, during preterm labour the infant's immune system was found to be activated specifically to attack the mother's cells.
Researchers detected higher levels of both dendritic cells and effector T cells in the cord blood of preterm infants; dendritic cells present foreign substances to the T cells to signify that they are a potential threat, and T cells - the primary fighter cells of the immune system - then mount an attack by releasing inflammatory chemicals.
T cells from preterm infants made significantly higher levels of these inflammatory chemicals, TNF alpha and interferon gamma, than those from full-term infants, and in a laboratory model of uterine contraction, the researchers discovered that these chemicals induced contraction of uterine cells.
"If you're a foetus and your immune system is developing in a healthy environment, it's in your best interest to keep things quiet so that you can develop and be born at a normal time," said Michela Frascoli, a former postdoctoral researcher in MacKenzie's lab.
"But if you encounter trouble in the form of an infection or inflammation, then that can trigger your dendritic cells and T cells to wake up. Ultimately, it could be a defense mechanism to exit a hostile uterine environment," said Frascoli, an assistant professor at the University of Massachusetts Medical School in the US.
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