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Passive Immunization against the MHC Class I Molecule Mamu-AG Disrupts Rhesus Placental Development and Endometrial Responses¹

Gennadiy I. Bondarenko^*, David W. Burleigh^2,*, Maureen Durning^*, Edith E. Breburda^*, Richard L. Grendell^* and Thaddeus G. Golos^3,*,

^* Wisconsin National Primate Research Center and Department of Obstetrics and Gynecology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI 53715

The unique MHC phenotype of the human and nonhuman primate placenta has suggested a potential role in maternal-fetal immune tolerance, pregnancy success, and maternal as well as fetal well-being. In the rhesus monkey (Macaca mulatta) a nonclassical MHC class I molecule, Mamu-AG, is a putative homologue of HLA-G and is hypothesized to play a role in maternal-fetal immune interactions during pregnancy. Rhesus monkeys were passively immunized during the second week after implantation with a mAb against Mamu-AG. Passive immunization altered the growth and vascularization of the fetal placenta, the placental modification of maternal endometrial vessels, the maternal leukocyte response to implantation, and the differentiation of epithelial and stromal cells in the endometrium. These data are the first to demonstrate in vivo the importance of MHC class I molecules expressed on primate trophoblasts in establishing an important environment for pregnancy success through coordinated interactions between endometrial and fetal tissues.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants HD37120 and HD34215 (to T.G.G.), and RR000167 (to Wisconsin National Primate Research Center).

² Current Address: Division of Natural Sciences and Mathematics, Richard Stockton College of New Jersey, Pomona, NJ 08240.

³ Address correspondence and reprint requests to Dr. Thaddeus G. Golos, Wisconsin National Primate Research Center, University of Wisconsin, 1223 Capitol Court, Madison, WI 53715. E-mail address: golos{at}primate.wisc.edu

⁴ Abbreviations used in this paper: STB, syncytiotrophoblast; 25D3, anti-Mamu-AG mAb; CG, chorionic gonadotropin; DC-SIGN, DC-specific ICAM3-grabbing nonintegrin; EVCT, extravillous cytotrophoblast; IHC, immunohistochemistry; NS, nonspecific; VEGF, vascular endothelial growth factor.

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The JI 2007 179: 7991-7992. [Full Text]  

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