Anti-P- and E-selectin therapy prevents abortion in the CBA/J × DBA/2J combination by blocking the migration of Th1 lymphocytes into the foetal-maternal interface

Institute of Medical Immunology, Charité, Medical University of Berlin, Berlin, Germany.
Cellular Immunology (Impact Factor: 1.92). 01/2006; 238(2):97-102. DOI: 10.1016/j.cellimm.2006.02.002
Source: PubMed


Leukocyte migration into inflamed tissues comprises dynamic interactions between immune and endothelial cells through events controlled by adhesion molecules, e.g., P- and E-selectins, which mediate Th1 cells recruitment after injury. Since miscarriage is known to be a Th1 event and selectins are expressed at the murine foetal-maternal interface, the purpose of our study was to investigate whether blocking P- and E-selectins before implantation could inhibit Th1 migration into the foetal-maternal interface and thus prevent foetal rejection. DBA/2J-mated CBA/J females were treated with monoclonal antibodies (mAbs) against P-selectin or with both, anti-P- and anti-E-selectins combined on days 2 and 4 of pregnancy. PBS-treated females served as controls. Our data revealed a significant improvement in pregnancy outcome in both treated groups compared to the control, which is due to the effectiveness of the mAb against P-selectin, since the treatment with anti-E-selectin alone could not prevent abortion. We further observed that there was diminished Th1 cytokine production by decidual immune cells in all treated groups in comparison to the controls. Our data first confirm the important role of P-selectin in mediating the extravasation of abortive cells, while opening new therapeutic opportunities.

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    • ") spontaneously provokes high abortion rates, whereas mating of CBA/J females with BALB/c mice, which also bear H2 d antigens, ends with completely normal pregnancies [13] [14]. With these backgrounds, the aim of the present work was to perform a simultaneous evaluation of immune states at the fetomaternal interface and systemic levels in CBA/J Â DBA/2 as abortion mouse model and CBA/J Â BALB/c as non-abortion mouse model or normal pregnancy control. "
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