A TRANSFORMING GROWTH-FACTOR-BETA-2 (TGF-BETA-2)-LIKE IMMUNOSUPPRESSIVE FACTOR IN AMNIOTIC-FLUID AND LOCALIZATION OF TGF-BETA-2 MESSENGER-RNA IN THE PREGNANT UTERUS

This report describes a murine amniotic fluid (MAF) immunosuppressive factor that has properties similar to transforming growth factor β (TGF-R). The MAP factor exhibits TGF-β-like activity in stimulating soft agar colony formation by AKR-2B cells and inhibiting thymidine uptake by Mv1Lu cells. We demonstrate that both the immunosuppressive and TGF-β-like activities ofthe MAP factor are completely neutralized by antiTGF-02-specific antibodies and not by anti- TGF-β1-specific antisera. The immunosuppressive factor in MAP is novel in that it appears to be identical or very closely related to TGF-β2 and is active in its native state. This active and antiTGF-β2-neutralizable factor chromatography at -70 kD on Sephadex at neutral pH and appears to be able to complex with ci-fetoprotein in native amniotic fluid. Chromatography of native MAP under acidic conditions demonstrates a lower molecular mass protein that chromatographs on BioGel in the same position as the mature 25-kD TGF-0. This protein has the biological properties of TGF-β and is immunosuppressive. Both of these activities are neutralizable with antiTGF-β2 but not with antiTGF-β1 or other antisera. By Northern analysis, we find high levels of TGF-β2 mRNA (with little or no TGF-β1) in the pregnant uterus that peak around day 15 of gestation and then fall rapidly by day 19 as birth approaches. The TGF-β2-like factor could possibly play a role in maternal immunity, in the retention of the fetal allograft, as well as in regulating fetal and neonatal immunological competence. © 1990, Rockefeller University Press., All rights reserved.