Editor’s summary
During pregnancy, some exchange of cells occurs between the mother and the offspring, with fetal cells persisting in small quantities in the mother (microchimeric cells) and, conversely, maternal microchimeric cells in the fetus. These cells help to promote the expansion of T regulatory cells that blunt the immune response and ensure that the mother’s immune system does not reject the fetus. Shao et al. tracked the persistence of maternal and fetal microchimeric cells in mouse models in multiple pregnancies sired by immunologically different fathers (see the Perspective by Porrett). The authors determined that fetal cells from a previous pregnancy persist in subsequent ones, whereas maternal microchimeric cells present in a daughter mouse get replaced by offspring cells when the daughter mouse becomes pregnant. —Yevgeniya Nusinovich
Abstract
Pregnancy confers partner-specific protection against complications in future pregnancy that parallel persistence of fetal microchimeric cells (FMcs) in mothers after parturition. We show that preexisting FMcs become displaced by new FMcs during pregnancy and that FMc tonic stimulation is essential for expansion of protective fetal-specific forkhead box P3 (FOXP3)–positive regulatory T cells (Treg cells). Maternal microchimeric cells and accumulation of Treg cells with noninherited maternal antigen (NIMA) specificity are similarly overturned in daughters after pregnancy, highlighting a fixed microchimeric cell niche. Whereas NIMA-specific tolerance is functionally erased by pregnancy, partner-specific resiliency against pregnancy complications persists in mothers despite paternity changes in intervening pregnancy. Persistent fetal tolerance reflects FOXP3 expression plasticity, which allows mothers to more durably remember their babies, whereas daughters forget their mothers with new pregnancy-imprinted immunological memories….
