This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To identify the function of MHC class I expression and endometrial NK cells at the maternal-fetal interface. During human and non-human primate pregnancy, the uterine endometrium differentiates into the decidua. Decidual NK cells are believed to play a key role in the development of a proper environment for placental growth by producing cytokines and angiogenic factors in response to nonclassical MHC class I molecules on the placental trophoblasts. These include HLA-G in human and Mamu-AG in the rhesus monkey. The majority of rhesus decidual NK cells are CD56+ cells, co-expressing CD16 and CD8. Anti-CD16 (3G8) mouse mAb and anti-CD8 (cM-T807) human-mouse chimeric mAb were used in non-pregnant and pregnant animals at day 18 of gestation. The efficiency of depletion was monitored by flow cytometry and animals were euthanized 7 days after treatment. The administration of anti-CD16 resulted in 62-87% depletion of peripheral blood NK cells;anti-CD8 treatment depleted 96-99% of peripheral blood NK cells, as well as peripheral blood CD8+ T cells, and resulted in placental abruption and signs of imminent pregnancy loss. Control treatments consisted of treatment with human intravenous immunoglobulin (hIVIg), or anti-CD20, a widely used B cell marker. Unexpectedly, there were signs of impending pregnancy loss in these animals as well. Analysis of peripheral blood and vaginal secretion cytokine levels suggested that pregnancy loss was not a nonspecific response to immunodepletion. Surprisingly, NK cell immunodepletion suggested that loss of decidual NK cells enhances, rather than increases extravillous endovascular trophoblast migration, but only in NK depleted animals, and not in control treated animals. Thus, pregnancy in rhesus monkeys is sensitive to immune perturbation, and provides a model to study recurrent pregnancy loss and control of endovascular trophoblast migration. This research used WNPRC Animal Services and Research Services. Note: Not AIDS related, but key words similar.
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