Induction of class II major histocompatibility complex antigens in murine placenta by 5-azacytidine and...

Class II MHC antigen expression is required for recognition of an alloantigen and generation of immune response. In rodents as well as in humans primary trophoblasts do not express class II MHC antigens. In this study we focused our interest on the mechanism(s) of class II antigen suppression on murine trophoblasts. First, we examined the possibility of gene inactivation by methylation and second the possibility of lymphokine regulation of the class II genes. The first possibility was tested by treatment of placental cells with 5-azacytidine (5-AzaC), a cytidine analog which upon incorporation into the DNA inhibits further methylation, thus leading to gene activation. In order to test the second possibility we treated placental cells with interferon-gamma (IFN-gamma) or interleukin 4 (IL4) which are known to induce class II antigen expression in many systems. We showed that treatment with 5-AzaC or IFN-gamma but not IL4 significantly increased class II expression on cytokeratin-positive and vimentin-negative adherent placental cells. Following placental cell fractionation we distinguished three cell subsets with different responsiveness to 5-AzaC and IFN-gamma. The first, characterized as placental macrophages, were induced to express class II MHC antigens only after IFN-gamma treatment. The other two subsets, characterized as trophoblasts, were isolated from the labyrinthine- and spongio-trophoblast layer of the placenta and showed class II inducibility to 5-AzaC and IFN-gamma, respectively. The results show that depending on the anatomical localization of trophoblasts within the placenta, various regulatory elements control gene expression, so that the placental barrier provides fetal protection at different levels.