Tolerance to noninherited maternal antigens in mice and humans.

Abstract

Exposure to noninherited maternal antigens (NIMAs) in fetal and neonatal life has life-long immunological consequences. Although there is a plethora of evidence of effects of mother on the immune responses of her offspring, there is very little knowledge available on how exposure to NIMA can result in either tolerance or sensitization. Understanding the mechanism of NIMA effects will impact different fields of immunology including transplantation, autoimmunity, and tumor immunotherapy. Following the discoveries of beneficial effects of NIMA exposure on clinical outcomes in solid organ and bone marrow transplantation, it has now been shown that the exposure to NIMA induces various types of T regulatory (T(R)) cells in fetus and adult, which may partially account for tolerance to allografts bearing the NIMA. Although all offspring are exposed to the maternal antigens, they exhibit a great variability in the NIMA effects, which can be explained by the variability in the extent of maternal microchimerism (MMc). Exposure to NIMA can have tolerogenic or sensitizing effects on the offspring, resulting in acceptance or rejection of allografts expressing the NIMA. This variability may be partly explained by the level and distribution of maternal cells persisting in the offspring.