Cellular Immunology 238 (2005) 97–102 www.elsevier.com/locate/ycimm 0008-8749/$ - see front matter  2006 Elsevier Inc. All rights reserved. doi:10.1016/j.cellimm.2006.02.002 ARTICLE IN PRESS 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 Annarosa Zambon Bertoja a , Maria Laura Zenclussen a , Pablo Ariel Casalis b , André Sollwedel a , Anne Schumacher a , Christian Woiciechowsky b , Hans-Dieter Volk a , Ana Claudia Zenclussen a,¤ a Institute of Medical Immunology, Charité, Medical University of Berlin, Berlin, Germany b Department of Neurosurgery, Charité, Campus Virchow Klinikum, Medical University of Berlin, Berlin, Germany Received 5 October 2005; accepted 6 February 2006 Abstract Leukocyte migration into inXamed tissues comprises dynamic interactions between immune and endothelial cells through events con- trolled 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 block- ing 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-selec- tins combined on days 2 and 4 of pregnancy. PBS-treated females served as controls. Our data revealed a signiWcant improvement in preg- nancy outcome in both treated groups compared to the control, which is due to the eVectiveness 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 Wrst conWrm the important role of P-selectin in mediating the extravasation of abortive cells, while opening new therapeutic opportunities.  2006 Elsevier Inc. All rights reserved. Keywords: Selectins; Th1/Th2 cytokines; Pregnancy 1. Introduction During pregnancy, the semiallogeneic foetus survives in the uterus despite the presence of maternal T cells speciWc to paternally inherited histocompatibility antigens. This is thought to be due to a transient tolerance state from mater- nal cells against paternal alloantigens [1]. Immune privilege is necessary for a successful pregnancy, thus lack of toler- ance may be partially responsible for pathologic conditions such as abortion [2–4]. As portrayed by the debatable Th1/ Th2 paradigm, predominance of anti-inXammatory Th2 cytokines (IL-4 and IL-10) over pro-inXammatory Th1 cytokines (IL-2, TNF-, and IFN-) at the foetal-maternal interface would support maintenance of pregnancy, while the prevalence of a Th1-type response hampers foetus sur- vival [5–11]. During spontaneous abortion, the migration of Th1 inXammatory cells into the foetal-maternal interface may be responsible for local inXammation and perpetua- tion of the injury until the complete rejection of the foetus is achieved. In the well-known CBA/J £ DBA/2J murine combination, in which the foetal rejection is thought to be MHC-restricted, minor loci dependent [12], augmented pro-inXammatory cytokines production has been widely * Corresponding author. Present address: Reproductive Immunology Group, Institute of Medical Immunology, BMFZ, Raum 2.0534, Augu- stenburger Platz 1, 13353 Berlin, Germany. Fax: +49 30 450 559986. E-mail address: ana.zenclussen@charite.de (A.C. Zenclussen).