Localization of IFN-gamma receptor in first trimester placenta to trophoblasts but lack of stimulation of HLA-DRA, -DRB, or invariant chain mRNA expression by IFN-gamma.
Trophoblasts do not express MHC class II Ag on their cell surface, but it is not known at which level the regulation of expression of these IFN-gamma-responsive genes occurs. We localized the IFN-gamma R Ag to the trophoblasts of normal human first trimester placenta. As previously shown, treatment with IFN-gamma of short term cultures of placental explants did not induce expression of HLA-DR Ag in trophoblasts. We demonstrated that in situ hybridization with probes for DRA, DRB, and MHC class II-associated invariant chain genes gave no detectable signals for the presence of the corresponding mRNA in cytotrophoblasts or syncytiotrophoblasts of first trimester placenta with or without IFN-gamma. Maternal leukocytes in these placental preparations as well as IFN-gamma-treated HeLa cell control cultures expressed these mRNA. In addition, Northern analysis of RNA isolated from the trophoblast cell line Jar after treatment with IFN-gamma showed that induction of transcription did not occur from the HLA-DRA, HLA-DRB, or invariant chain genes. Jar cells expressed the IFN-gamma R Ag. These data suggest that down-regulation of MHC class II Ag on trophoblasts in the first trimester placenta and in a cell line include a lack of productive intracellular signaling by the IFN-gamma R and maintenance, in a coordinate manner, of low steady state levels of the mRNA encoded by the DRA, DRB, and invariant chain genes.
Peyman
J A
JA
Department of Surgery, Yale University School of Medicine, New Haven, CT 06510.
Hammond
G L
GL
D000944:Antigens, Differentiation, B-Lymphocyte; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012333:RNA, Messenger / Q000032:analysis*; D017471:Receptors, Interferon / Q000032:analysis*; D014327:Trophoblasts / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D000944:Antigens, Differentiation, B-Lymphocyte; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D017471:Receptors, Interferon; C045084:invariant chain; D007371:Interferon-gamma