Microchimeric cells, which are fetal cells present in mothers and maternal cells in fetuses, have long intrigued scientists for their role in promoting immune tolerance during pregnancy. A recent study by Shao et al. delved into the dynamics of these microchimeric cells and their effects on subsequent pregnancies. Their findings shed light on the enduring influence of these cells on reproductive outcomes.
During pregnancy, a bidirectional exchange of cells occurs between the mother and the developing fetus. This exchange results in the presence of fetal microchimeric cells (FMcs) in the mother and maternal microchimeric cells in the fetus. These microchimeric cells play a crucial role in immune regulation, preventing the mother’s immune system from rejecting the fetus.
The study conducted by Shao et al. used mouse models to investigate the persistence of maternal and fetal microchimeric cells in multiple pregnancies, particularly in cases involving different fathers. Their research revealed several noteworthy findings.
Firstly, the study demonstrated that FMcs from previous pregnancies continue to exist in subsequent pregnancies, highlighting their long-lasting presence in the maternal body. This persistence contributes to the expansion of fetal-specific regulatory T cells (Treg cells), which play a crucial role in immune regulation.
Secondly, maternal microchimeric cells present in a daughter mouse are gradually replaced by offspring cells when the daughter mouse becomes pregnant. This observation suggests the existence of a fixed microchimeric cell niche within the body.
The research also highlighted the intriguing phenomenon of partner-specific protection conferred by pregnancy. Despite changes in paternity between pregnancies, mothers retained partner-specific resilience against pregnancy complications. This resilience was attributed to the persistent presence of FMcs and the expansion of Treg cells with fetal-specific forkhead box P3 (FOXP3) expression.
In contrast, daughters who became pregnant experienced a shift in their immunological memory. Their maternal microchimeric cells were replaced by new pregnancy-imprinted immunological memories, erasing noninherited maternal antigen (NIMA)-specific tolerance.
Overall, this study emphasizes the enduring impact of microchimeric cells on reproductive outcomes and immune regulation. It reveals the remarkable plasticity of FOXP3 expression and its role in maternal-fetal immune interactions. While mothers retain lasting memories of their babies, daughters form new immunological memories with each pregnancy.
These findings provide valuable insights into the intricate interplay of microchimeric cells during pregnancy and their influence on maternal and fetal immune responses.