Dr. Margaret Petroff’s laboratory addresses two main, interrelated questions in the areas of reproductive immunology. The first relates to the immunological paradox of pregnancy: the survival of the semiallogeneic fetus in an immunologically foreign environment – the mother. Specific attention is paid to the immunomodulatory proteins belonging to the B7 family, which are highly expressed in the placenta. These proteins serve as ligands to receptors that are present on T lymphocytes, and ligation of their receptors confers either costimulation or inhibition of antigen-specific responses in T cells. Ongoing studies dissect local and systemic influences of placental B7s on maternal T cells, facilitated by recent findings that the placenta releases large quantities of exosomes carrying these proteins into the maternal circulation. Related efforts in the lab have expanded on the observations that in both mice and women, maternal T cells respond to specific fetal antigens that are expressed in the placenta. Indeed, the placenta is a rich source of fetal antigens, including paternally inherited minor histocompatibility antigens and tumor antigens. The Petroff lab is performing studies to determine the short and long-term functional consequences of maternal reactivity of these antigens, with particular attention to effects of antigenic load and the surrounding endocrine, oxygen and inflammatory environments. The second major project in the Petroff lab is based on the recently identified transcriptional regulator AIRE (AutoImmune Regulator), mutations of which, in humans, cause a monogenetic autoimmune disease, Autoimmune Polyglandular Syndrome type 1. In both humans and mice, the absence of functional AIRE results in organ-specific autoimmune disease due to the emigration of autoreactive T cells from the thymus. Dr. Petroff is using Aire knockout mice to identify the immunological basis of infertility in females and males lacking this protein. Collectively these projects, all of which both use mouse and human models, have direct relevance to human conditions of infertility, pregnancy failure, autoimmune disease, transplantation, and cancer immunology.