Tolerance Induction Following In Utero Stem Cell Transplantation

Abstract

One of the central tenets underpinning the science of immunology is the concept that the immune system is able to recognise “self tissues and consequently, to distinguish “self” from “non-self”. This ability to discriminate, even at a subtle molecular level, confers powerful protective functions on the immune system because invasion from without, by potentially harmful pathogenic agents, can be repulsed very effectively by various interacting arms of this host defence system. Dogma asserts that the tolerance to self tissues is learned in utero, during embryonic/fetal development (Billingham et al. 1953). Thus, as the immune system itself develops, the repertoire essential to effect host defence in postnatal life — the ability to discriminate between self and non-self — becomes indelible. However, there is a period in human fetal development when the immune system can be considered to be naive, that is, without full competence to discriminate it is unable to mount an immune response and would therefore leave the developing fetus vulnerable to invasion from without. This period, essentially during the first trimester of (human) fetal life, is predominantly prior to the phase at which passive immunity can be conferred via transfer of maternal immunoglobulins. Under normal circumstances, the uterine environment protects the fetus from infection, and development of immunocompetence can, therefore, proceed without impediment.