Cincinnati Children’s Researchers Uncover How Moms’ Immune Systems ‘Remember’ Prior Pregnancies

Findings from infectious disease researchers at Cincinnati Children’s shed new light on how a woman’s immune system adjusts during and after pregnancy. The implications of this work could also impact high-risk pregnancies, organ transplantation and vaccine research.

A research team led by Sing Sing Way, MD, PhD, published their study “Reproductive outcomes after pregnancy-induced displacement of preexisting microchimeric cells” in the journal Science.

It’s known that pregnancy requires a mother’s body to adjust so that her immune system does not attack the growing fetus as if it were a hostile foreign invader. While scientists are growing their understanding of the immunology of pregnancy, this new study shows that the cellular crosstalk between a mother and her offspring is even more complex and long-lasting than expected.

“By investigating how prior pregnancy changes the outcomes of future pregnancies—or how mothers remember their babies—our findings add a new dimension to our understanding of how pregnancy works,” Way says. “Nature has designed built-in resiliency in mothers that reduces the risk of preterm birth, preeclampsia and stillbirth in women who have had a prior healthy pregnancy. If we can learn ways to mimic these strategies, we may be able to design improved therapies to prevent complications.”

How Moms Remember Their Babies

Earlier studies by Way’s team found that the experience of a first pregnancy makes a woman’s body much less likely to develop complications in subsequent pregnancies with the same father.

Researchers discovered the mother’s body keeps a longer-term supply of immune-suppressive T cells that recognize the next fetus by the same couple. These T cells tell the immune system to stand down as the pregnancy develops. They also linger in the mother’s body for years after giving birth.

For immunity against infection, “memory” cells require a constant, low level of exposure to the invading pathogen. That’s why it was surprising to find the suppressive T cells in mothers well beyond childbirth.

The new study shows that tiny populations of baby cells remain in mothers after pregnancy. Called fetal microchimeric cells, these baby cells can maintain protective memory-suppressive T cells in mothers long after pregnancy.

“Very small numbers of fetal cells can be found in the heart, liver, intestine, uterus and other tissues,” Way says. “We are made up of cells with our own genetics, and cells from our mothers and our children. It’s a fascinating idea.”

This latest work builds on previous findings from Way and colleagues that show children maintain a small supply of cells from their mothers—called maternal microchimeric cells. These cells explain why an organ transplant from a person’s mother is more likely to be successful than a donor organ from the father.