LOCALIZATION OF IL-4 AND IL-4 RECEPTORS IN THE HUMAN TERM PLACENTA, DECIDUA AND AMNIOCHORIONIC MEMBRANES

There has been much recent interest in cytokine expression at the mate rno-fetal interface. Although T-helper 2 (Th2)-type cytokines have bee n described in the murine fete-placental unit, few studies have as yet been performed in human pregnancy. We have examined the production of interleukin-4 (IL-4) and expression of IL-4 receptors in the human te rm placenta, decidua and amniochorionic membranes. Immunohistochemical analyses revealed that cytotrophoblast, decidual macrophages and both maternal and fetal endothelial cells consistently expressed IL-4, whe reas syncytiotrophoblast and placental macrophages showed an inconsist ent pattern between specimens. High- and low-affinity IL-4 receptors w ere demonstrated by immunohistochemistry at the same cellular sites as stained for IL-4, and detection of IL-4 receptors was also variable i n syncytiotrophoblast. Reverse-transcribed-polymerase chain reaction ( RT-PCR) analysis showed that both IL-4 and its alternative splice vari ant, IL-4 delta 2, are produced both in placental villi and in amnioch orionic and decidual tissue. Ligand-binding assays identified the pres ence, on isolated term syncytiotrophoblast microvillous plasma membran e vesicle preparations, of functional high-affinity binding sites for IL-4 with a Kd in the range 102-112 pM and an apparent receptor densit y in the rangE 99-102 x 10(8) sites/mg protein. Three human choriocarc inoma (BeWo, JEG-3 and Jar) and one amnion-derived (AV3) cell lines ex pressed IL-4 and both high- and low-affinity IL-4 receptors. The const itutive expression of both IL-4 and IL-4 receptors, together with the novel finding of the alternative splice variant IL-4 delta 2 in the im mediate tissues at the materno-fetal interface suggest an immunobiolog ical role for IL-4 in human pregnancy.