Every human born on this planet is not entirely themselves.
A tiny fraction of our cells – around one in a million – is actually not our own, but comes from our mothers. That means each of us has millions of cells that our immune systems would normally recognize as foreign; yet somehow, in most of us, they hang around peacefully without causing any immune problems.
Now, immunologists have figured out why. A small number of maternal immune cells that cross the placenta during pregnancy actively train the fetus's immune system to tolerate the mother's cells for their entire life.
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The exchange of cells between a mother and a fetus is a well-documented phenomenon that scientists have known about for more than 50 years. It's called microchimerism, and it goes both ways: every human who has ever been pregnant retains cells from their fetus, and every human retains cells from their mother.
These lingering cells pose a puzzle for immunology, which is built around the idea that the immune system should mount an attack against foreign cells.
A team led by pediatric infectious disease specialist Sing Sing Way of Cincinnati Children's Hospital Medical Center wanted to understand more about how these foreign maternal cells keep the immune system in check, and what role they play in shaping the fetus' immune system.
To find out, the researchers studied maternal microchimerism in mice. Building on their previous studies, the researchers bred mice with immune cells engineered to express specific cell surface markers. This allowed researchers to selectively deplete those cells and see whether or not immune tolerance was maintained.
Here's where it got fascinating. A small subset of the maternal immune cells, with properties similar to bone marrow myeloid cells and dendritic cells, persisted long after birth. They were also strongly associated with both immune activity and the expansion of regulatory T cells – the cells that tell the immune system that everything is copacetic.
To confirm, the researchers next selectively edited out those specific maternal cells in offspring mice.
The results were dramatic. The regulatory T cells disappeared, and the immune tolerance of maternal cells disappeared.
The implication is that lifelong tolerance to maternal microchimeric cells is probably dependent on just a tiny subset of maternal cells. Take those away, and immune chaos likely ensues. That also means that immune tolerance needs to be continuously and actively maintained; it's not a one-and-done process during pregnancy.
That's interesting and exciting in its own right, but the research also offers a way to gain a greater understanding of the broad swath of diseases and conditions to which microchimerism may contribute.
"The new tools we developed to study these cells will help scientists pinpoint exactly what these cells do and how they work in a variety of contexts including autoimmune disease, cancer and neurological disorders," Way says.
"Microchimerism is increasingly linked with so many health disorders. This study provides an adaptable platform for scientists to investigate whether these rare cells are the cause of disease, or alternatively, found in diseased tissue at increased levels as part of the natural healing process."
The research has been published in Immunity.