17:20-17h30 Prenatal transfer of pathogen-specific maternal microchimeric cells to the fetus

During mammalian pregnancy, maternal cells can be transferred across the placenta to the fetus. The cells can be retained in the offspring until adulthood and are referred to as maternal microchimeric cells (MMc). It was recently demonstrated that MMc can protect neonates from infections. To further elucidate the immunological impact of MMc on offspring’s risk for infections, we here tested if MMc also include cell subsets of pathogen specificity. Non-pregnant C57BL/6J female mice were immunized with 104 CFUs of recombinant Listeria monocytogenens expressing ovalbumin (LmOVA) and allogenically mated with BALB/c males after infection was cleared. At gestational day 18.5 single-cell suspensions of fetal spleen, liver and bone marrow were prepared. After enrichment of MMc using magnetic-activated cell sorting (MACS), resulting cell suspensions were analysed via flow cytometry. For identifying Listeria-specific MMc, an OVAspecific MHC-Tetramer was used. Additionally, pregnancy outcome data such as fetal weight, placental ratio and Lm-antibody status were assessed. In a follow-up experiment, neonates were re-infected at day 7 after birth using 104 CFUs of a recombinant Listeria monocytogenes strain lacking the ActA protein (LmOVA ΔactA). Neonatal liver and spleen were analysed at experimental day 7 post infection using the methods described above. We identified that Listeria-specific T cells were transferred across the placenta from the mother to the fetus, generating a pathogen-specific MMc-subset, which colonized the fetal bone marrow, spleen and liver. Fetuses harvested from infected and subsequently pathogen-cleared mothers showed a lower body weight one day before birth, but caught up with control litter after birth during early neonatal phase. After re-infection with LmOVA ΔactA, neonates born to a previously LmOVA-infected, recovered mother show less reduction in weight compared to the neonates born to uninfected mothers. Our present study shows that pathogen-specific T cells can be transferred from the mother to the fetus during pregnancy. We hypothesize that these pathogen-specific cells are memory T cells, which could mitigate neonatal immunity in a pathogen-specific manner and exceed any protection mediated by passive immunity. Whether those cells directly protect the offspring from infections or help to shape the immune system in an indirect manner, i.e. by interacting with fetal immune maturation, is subject of ongoing research. Our findings amend the well-known transfer of antibodies from mother to offspring, thereby broadening the classical understanding of cross-generational immunological memory.