A transforming growth factor β2 (TGF-β2)-like immunosuppressive factor in amniotic fluid and localization of TGF-β2 mRNA in the pregnant uterus

Abstract

This report describes a murine amniotic fluid (MAF) immunosuppressive factor that has properties similar to transforming growth factor β (TGF-β). The MAF 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 of the MAF factor are completely neutralized by anti-TGF-β2-specific antibodies and not by anti-TGF-β1-specific antisera. The immunosuppressive factor in MAF 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 anti-TGF-β2-neutralizable factor chromatographs at ∼70 kD on Sephadex at neutral pH and appears to be able to complex with α-fetoprotein in native amniotic fluid. Chromatography of native MAF under acidic conditions demonstrates a lower molecular mass protein that chromatographs on BioGel in the same position as the mature 25-kD TGF-β. This protein has the biological properties of TGF-β and is immunosuppressive. Both of these activities are neutralizable with anti-TGF-β2 but not with anti-TGF-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.