Placenta-Derived Exosomes and Their Role in the Immune Protection of the Fetus

The mammalian pregnancy is an immunologic challenge to the maternal immune system. Considering the fact that transplant rejection is a well-defined immunologic phenomenon, the peaceful feto-maternal coexistence during mammalian pregnancy has been defined as “a paradox of nature” and puzzled immunologists for ages. In 1953, the immunologist and Nobel Prize laureate Sir Peter Medawar proposed that the maternal immune system is ignoring the fetus and defined his three well-known mechanisms for achievement of this: anatomical separation of the fetus and the mother, fetal antigenic immaturity and maternal inertness or indolence to the fetus (1). Although Medawar’s proposal is still recognized and cited, it is only partly true and has been rightly revised in recent years. Today, it is wellproven that instead of being ignored, pregnancy is indeed recognized but tolerated by the maternal immune system, however, the responsible mechanisms for that remain unknown. The maternal-fetal interactions are highly complex and cannot be explained by, or subordinated to a single uniting theory of maternal tolerance to the fetus. In stead, multiple mechanisms, operating in concert at the systemicas well as the local level are moulding the framework of successful pregnancy (reviewed in 2). Several of these mechanisms are mediated by the placenta, the key organ for successful mammalian reproduction (2).