CELLULAR-LOCALIZATION OF CD4 IN THE HUMAN PLACENTA - IMPLICATIONS FORMATERNAL-TO-FETAL TRANSMISSION OF HIV

CD4 is a 55-kDa glycoprotein that serves as an important cellular diff erentiation Ag and cell signaling protein on T lymphocytes, as well as a principal receptor for HIV-1 on a variety of cell types including l ymphocytes. CD4 receptor expression in syncytiotrophoblasts, the princ ipal cellular barrier in the human placenta, has not been clearly defi ned. Knowledge concerning the expression of the CD4 receptor on placen tal trophoblasts is important to define potential mechanisms of transm ission of the virus between maternal blood and fetal tissues. Both mat ure and immature placenta (n = 10) were examined using an avidin D-bas ed immunohistochemical procedure that permits clear morphologic distin ction of cell types in placental sections. Syncytiotrophoblasts were d efined using anti-cytokeratin mAb (AE1/3), whereas endothelial cells i n placental villi were distinctly identified using a mAb directed to C D31. Placental Hofbauer cells (macrophages) and other leukocytes were identified by mAb staining of leukocyte common Ag (CD45). CD4 expressi on (identified by staining with three separate anti-CD4 mAb) was exclu sively localized using this immunohistochemical method to leukocytes i n placental villi (e.g., Hofbauer cells); however, no CD4 staining was evident in syncytiotrophoblasts, cytotrophoblasts, or villus endothel ial cells. Furthermore, immunoaffinity-purified trophoblasts were nega tive for CD4 receptor expression. CD4 RNA was not identified in purifi ed trophoblasts using both Northern blot assay and a sensitive polymer ase chain reaction method to identify CD4 RNA. In addition, time cours e studies of purified trophoblasts immediately after purification and at 24, 48, and 72 h in culture indicated that CD4 RNA was not present as a transient, but labile transcript in trophoblasts. These data indi cate that the transmission of HIV-1 across syncytiotrophoblasts may oc cur by mechanisms other than by binding the CD4 receptor and that tiss ue leukocytes (in particular Hofbauer cells) are likely the principal CD4+ cellular target of HIV-1 in the placenta.