This is a proposal to continue studies into the role of local immune regulation in preventing a maternal anti-fetal immune rejection. The underlying rationale is that the system may at times fail, leading to spontaneous abortion. Understanding the mechanisms may be important to decreasing the incidence of such failures. The operating theory is that protection of the developing embryo results from a combination of the immunologically inert physical barrier provided by the trophoblast and a region of local immunosuppression generated in the uterus around the fetus. This environment is generated during the decidual response through a massive increase in numbers of prostaglandin producing cells, principally macrophages. To explore this hypothesis, it is proposed that a study be performed of: 1) Control mechanisms influencing macrophage accumulation in the uterus during pregnancy, 2) Mechanism(s) responsible for immunoregulation by decidual macrophages, 3) The extent and nature of immunoregulation in uterine regional lymph nodes, 4) A model of indomethacin induced abortion which is closely relevant to the proposed immunoregulatory mechanisms. The above specific aims will be studied using a variety of cellular immune techniques in a mouse model system. In conclusion, these studies should lead to an extension of current knowledge of the immunology of pregnancy.
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