IFN-gamma facilitates release of class II-loaded intracellular pools in trophoblast cells: A novel property independent of protein synthesis

Interferon-gamma (IFN-gamma) is an abortion-inducing factor, yet its effect s in such a reaction are subject to various levels of regulation. The troph oblast cell line TROPHO-1 can be induced by IFN-gamma to express mRNA and s urface class II major histocompatibility complex (MHC) proteins after 8 and 48 h of stimulation, respectively. Untreated cells, however, show an intra cellular accumulation of class II antigens earlier (6 h), indicating the ex istence of MHC pools in the cystosol independent of any induction. On addit ion of IFN-gamma, immunofluorescence, subcellular fractionation, and ELISA experiments showed that class II antigen activity detected in the endosomal compartments of the cells could be measured in the culture supernatants. T hese soluble class II proteins, when isolated and purified using magnetic b ead isolation techniques and tested in SDS-PAGE gel and Western blot experi ments, had a molecular weight of 70 kDa, Administration of these molecules to pregnant mice as culture supernatants increased the abortion rate and de creased maternal hematocrit levels, effects that could be immunoabsorbed by anti-I-A(d) monoclonal antibodies (mAb), These results indicate that altho ugh surface class II molecules are not expressed on trophoblast cells, they accumulate in endosomal compartments and can be released from the cells on addition of IFN-gamma, This new IFN-gamma property, to mobilize intracellu lar pools of class II MHC antigens in trophoblast cells independent of de n ovo protein synthesis and induce their release to the extracellular matrix, is a mechanism that appears to be involved in the fetal rejection process, facilitating priming of the maternal organism against the fetal allograft.