The lack of immune rejection during pregnancy provides an opportunity to study specific regulatory mechanisms of the immune response pertaining to both humoral and cellular interactions. Pregnancy in mammals acts much like a tissue graft, with the time of implantation bringing into direct contact two genetically dissimilar tissues. However, in this unique instance, there is no detrimental immune rejection towards the fetoplacental unit. The suggested causes for this lack of immune response include that the uterus is an 'immunologically privileged site', a lack of antigen on embryonic tissues, a physical barrier separates maternal and fetal tissues, immunoabsorption by placenta, a local high concentrations of protein and steroid hormones, and localized immune suppressor cells in and adjacent to the tissues of the placenta. Each of these factors may contribute to the preservation of the fetus, however, our previous work indicates that specific monoclonal antibodies against antigen specific T-cell suppressor factors is detrimental to the continuation of pregnancy when injected into pregnant mice. Further investigation with this monoclonal antibody in competitive inhibition ELISA assays for uterine content of T-cell suppressor factors indicate that there is an increase in amount at the time of implantation (either normal Day 5 of pregnancy or experimentally induced implantation) and that when implantation is delayed there is a decreased level of T-cell suppressor factors. Implantation is an estrogen triggered event in the mouse and thus, we propose to examine the role of antigen specific T-cell suppressor factor at the time of implantation and determine both the influence of the steroid hormones and the presence of an implanting blastocyst on levels of T-cell suppressor factor. Examination of antigen specific T-cell suppressor factor will be undertaken during early stages of implantation in ovariectomized mice synchronized by steroid replacement therapy. Examination of the effect of steroids in both pregnant and nonpregnant animals, as well as, the examination of the immune suppression caused by co-incubation of blastocysts in mixed lymphocyte cultures, will allow separation between steroid, embryo, and steroid-embryo interaction. Increasing our understanding of the regulation of the immune system at the time of implantation, a critical time during pregnancy, will increase our understanding of the immunoregulatory mechanisms that are brought into play throughout pregnancy and allow an examination of causes of fetal wastage.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Reproductive Biology Study Section (REB)
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Indiana University-Purdue University at Indianapolis
Anatomy/Cell Biology
Schools of Medicine
United States
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