A transforming growth factor beta 2 (TGF-beta 2)-like immunosuppressive factor in amniotic fluid and localization of TGF-beta 2 mRNA in the pregnant uterus.

Abstract

This report describes a murine amniotic fluid (MAF) immunosuppressive factor that has properties similar to transforming growth factor .beta. (TGF-.beta.). The MAF factor exhibits TGF-.beta. like activity in stimulating soft agar colony formation by AKR-2B cells and inhibiting the thymidine uptake by Mv1Lu cells. We demonstrate that both the immunosuppressive and TGF-.beta.-like activities of the MAF factor are completely neutralized by anti-TGF-.beta.2-specific antibodies and not by anti-TGF-.beta.-specific antisera. The immunosuppressive factor in MAF is novel in that it appears to be identical or very closely related to TGF-.beta.2 and is active in its native state. This active and anti-TGF-.beta.2-neutralizable factor chromatographs at .apprx.70 kD on Sephadex at neutral pH and appears to be able to complex with .alpha.-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-.beta.. This protein has the biological properties of TGF-.beta.2 but not with anti-TGF-.beta.1 or other antisera. By Northern analysis, we find high levels of TGF-.beta. mRNA (with little or no TGF-.beta.1) in the pregnant uterus that peak around day 15 of gestation and then fall rapidly by day 19 as birth approaches. The TGF-.beta.2-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.