Neonatal tolerance: applicability to solid organ transplantation.

Abstract

The phenomenon of tolerance induced during immunologic immaturity has been explored for more than 60 years. Although direct application of neonatal tolerance to organ transplantation in human newborns is limited, exploiting discrete components of neonatal immaturity is proving fruitful. Two reviews comprehensively considered features and impact of neonatal tolerance as described in the 1950s. Recent imaging studies in mice demonstrated complex functional interactions especially of donor regulatory T cells with emerging neonatal immune components. The propensity of the developing immune system toward tolerance rather than immunity to non-self carbohydrates in ABO-incompatible transplantation was shown using glyconanotechnology tools to have exquisite specificity, and is associated with age-related changes in the B-cell compartment and complement components. Discarded infant thymus was found to be a source of abundant therapeutic regulatory T cells. Erythroid precursors transiently present in newborn mice and humans were shown to have immunosuppressive properties that may contribute to a tolerogenic environment. Neonatal tolerance has profound impact on immunology well beyond transplantation. Continued exploration of mechanisms underlying the malleability of the developing immune system and exploitation of particular components are leading to tools for immune manipulation beyond infancy.