How we achieve tolerance for our mothers: evidence for a layered immune system in humans (64.1)

Abstract

The developing fetal and neonatal immune system is known to be exceedingly prone to tolerance induction following exposure to foreign antigens. In mice this has been partially attributed to the absence of a functional adaptive immune system prior to birth. By contrast, the adaptive immune system is highly developed in human beings as early as the second trimester of fetal gestation. Nonetheless, evidence for intrauterine tolerance to non-inherited maternal alloantigens has been observed in clinical studies suggesting that the human fetal immune system is also prone to tolerance induction. In these studies we provide the first evidence for a mechanism underlying the development of immunological tolerance in human beings involving the generation of fetal CD4+CD25+ regulatory T cells (TReg) in the fetal peripheral lymphoid tissues. Additionally we provide evidence that the tolerogenic properties of the fetal adaptive immune system are in part attributed to the presence of a unique population of fetal T cells distinct from those found after birth. Our findings suggest that fetal hematopoietic stem cells (HSC) give rise to phenotypically and functionally distinct T cells than those derived from adult HSC. These findings have significant implications for many different clinical settings including intrauterine infections, transplantation, and autoimmunity.