Other - immune development
It has been thought that the immune system is immature and naïve at birth. A third of neonatal deaths are attributed to infections and newborns have reduced vaccine responses. Yet, most newborns are healthy. There is limited data on human in utero mucosal immunity. We performed deep immunophenotyping with CyTOF and T and B-cell receptor repertoire analysis with Next generation sequencing (NGS) in discarded spleen, liver and small and large intestinal samples from 20 fetuses (16-23 weeks’ gestation (GA)) and 5 neonates. We demonstrate that intestinal, hepatic and splenic immunity are unique to the organs, complex and functional at 16 weeks’ gestation (GA). B/TCR repertoires are diverse in fetal samples, with an increase in CDR3β/H length and distance-from-germline with advancing GA. Intestinal innate immunity is dominated by APCs, including CD103+DCs, ILCs and NK cells, whereas the liver and spleen innate compartments are made up mostly of APCs. Follicular and transitional B-cells are enriched in the fetal and CD69+IgM+B-cell in neonatal intestinal tissue. Yet the liver tissue contains few B and T-cells and the spleens contain abundant naïve B-cells. Greater than 50% of the fetal intestinal tissue leukocytes, but not those from the spleen or liver, are T-cells with majority being memory T-cells. Finally, functional tissue resident memory T-cells are abundant in the intestines but not the other tissues. Our data provide the foundation for a second trimester mucosal immune atlas and suggest that intestinal development occurs significantly earlier than previously reported.