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. Depletion of peripheral blood NK cells caused consistent placental dislocation and rapid pregnancy loss concomitant with reduced endometrial leukocyte populations, wheresas nonspecific antibody treatment, although associated with some pregnancy disruption, did not alter decidual leukocyte populations. Treatment of animals two weeks later, at days 29-35 of pregnancy, surprisingly did not induce pregnancy disruption, although there was a significant reduction in decidual NK cell numbers. These results suggest that the immunologic disruption of pregnancy is dependent on the developmental stage of gestation. This research used WNPRC Animal, Research, Assay, and Immunology &Virology Services. PUBLICATIONS: Drenzek J.G., Vidiguriene J., Vidiguris G., Grendell R.L., Dambaeva S.V., Durning M., and Golos T.G. 2009. Suppression of Mamu-AG by RNA interference. Am. J. Reprod. Immunol. 61: 453?461. Golos, T.G., Bondarenko G.I., Dambaeva, S.V., Breburda, E.E., Durning, M. 2010. On the role of placental major histocompatibility complex and decidual leukocytes in implantation and pregnancy success using non-human primate models. Int. J. Dev. Biol. 54:431-443. Note: AIDS-related.
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