Evidence of specialized leukocyte-vascular homing interactions at the maternal/fetal interface

In normal pregnancy, the maternal immune system fails to reject the fetus o r the placenta as an allogeneic graft. We hypothesize that specialized mech anisms of leukocyte recruitment might limit access of circulating maternal immune cells to the maternal/fetal interface. During the critical period of initial trophoblast invasion there is an elegantly orchestrated progressio n of leukocyte homing events in the decidua basalis, associated with highly regulated expression of vascular addressins and segregation of specialized leukocyte subsets into well-defined decidual microdomains. Neutrophils are limited to the region of necrosis associated with enzymatic digestion at t he leading edge of the invading trophoblast, where an almost linear array o f maternal blood Vessels displays the neutrophil ligand E-selectin. Cells w ith the phenotype of monocytes but expressing alpha 4 beta 7 integrin are l ocalized in the blood vessels of the specialized "vascular zone", which dis play the unusual combination of P-selectin (partially associated with plate lets) and the alpha 4 beta 7 ligand mucosal vascular addressin-l (MAdCAM-1) . Granulated metrial gland cells (alpha 4(+)beta 7(-), probably alpha 4 bet a 1(+)) constitute a well-defined cluster positioned in the central decidua basalis around venules prominently expressing the alpha 4 beta 1 ligand VC AM-1 (but not MAdCAM-1). T and B lymphocytes are rare. Our results suggest that selective mechanisms for regulating leukocyte access, associated with microdomain specialization within the decidua basalis, may play a fundament al role in immune regulation during the invasive period of placental develo pment.