October 13, 2025 | By Asher Jones
Pregnancy is a delicate balance for a mother’s immune system. Her immune cells must simultaneously recognize and eliminate invaders such as bacteria and viruses while tolerating the developing fetus.
“Pregnant mothers are essentially carrying a foreign organ,” said Jing Li, assistant professor of immunology in the School of Medicine and UPMC Hillman Cancer Center. “While half of the genetic material comes from the mother, the other half is from the father, which could trigger an immune response. If this response isn’t properly controlled, it can lead to miscarriage and other pregnancy complications.”
In a new Science Translational Medicine study, Li and her colleagues found that immune cells called KIR+ CD8+ T cells are elevated during pregnancy and play a role in suppressing overactive immune responses that could harm the fetus. The findings suggest that these cells could serve as biomarkers or potential therapeutic targets for pregnancy disorders.
Li, senior author Mark Davis, professor of microbiology and immunology at Stanford University, and their team previously discovered that human KIR+ CD8+ T cells play a role in limiting autoimmune disorders such as celiac disease, multiple sclerosis, and lupus. Similar to regulatory T cells, whose discovery earned the 2025 Nobel Prize in Physiology or Medicine, KIR+ CD8+ T cells suppress immune attacks on healthy tissue.
To learn whether these cells could also play a role in pregnancy, the researchers compared the blood of pregnant individuals with age-matched non-pregnant counterparts. They found that KIR+ CD8+ T cells were higher in pregnant people and increased during the second trimester.
“Interestingly, we found that women carrying male fetuses had higher levels of KIR+ CD8+ T cells than those carrying female babies,” said Li. “This is likely because the Y chromosome represents an additional element that is recognized as foreign by the mother’s immune system.”
The researchers took T cells from mothers and combined them with umbilical cord cells from their babies — donated to the Magee Obstetric Maternal and Infant (MOMI) Biobank at UPMC after delivery — in a dish. When KIR+ CD8+ T cells were removed, the mothers’ other T cells reacted much more strongly to the fetal cells, demonstrating their critical role in suppressing maternal immune responses against the fetus.
KIR+ CD8+ T cells were elevated in women who experienced miscarriage and preeclampsia, a potentially life-threatening condition characterized by persistently high blood pressure.
“It’s not that these cells are causing the problem,” said Li. “We believe that they’re trying harder to suppress an overactive immune response, but they may not be functioning efficiently enough.”
According to Li, KIR+ CD8+ T cells could serve as biomarkers to identify women at risk for pregnancy complications. In the future, therapeutic use of these cells might also suppress harmful immune responses in at-risk pregnancies.
Li hopes to continue this research at Pitt.
“Pregnancy is understudied compared to other fields,” she said. “Many people don’t think of it as an immunological question, focusing instead on fetal development. But understanding the maternal immune system is crucial to our understanding of pregnancy complications and improving outcomes for women and their babies.”
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Image 1: Jing Li, assistant professor of immunology in the School of Medicine and UPMC Hillman Cancer Center [Courtesy of Jing Li]
Image 2: KIR+ CD8+ T cells increase in a pregnant mother’s body during pregnancy. These cells help maintain a healthy pregnancy by suppressing alloreactive T cells, which recognize fetal proteins as foreign, a process that can potentially harm the fetus. [Credit: Made with BioRender]