A Mouse Placental Immunoregulatory Factor Different from Transforming Growth Factor β

Abstract

Of the growth-promoting factors, transforming growth factor β (TGF-β) has been most clearly shown to act as a potent regulator of inflammation and immunity. It is highly suppressive for T and B lymphocyte proliferation, cytotoxic T lymphocyte generation, and lymphokine-activated killer cell development, as well as natural killer cell activity. Moreover, there is accumulating evidence that TGF-β also may contribute to impaired immune surveillance of tumor development. In previous work, we isolated and described a 40 kD glycoprotein extracted from mouse placenta. This placental factor (PF) is also a potent immune modulator in vivo: it is highly inhibitory of secondary antibody responses as well as cellular responses, such as local graft-versus-host reactions. Because placenta has been shown to be a major source of TGF-β and several reports have indicated an important role for TGF-β in the immunosuppressive mechanisms taking place during the course of mammalian gestation, we have looked for the presence of TGF-β in our placental factor preparations. Our results clearly indicate that they do not contain TGF-β or TGF-β-like molecules by the following criteria: (1) no inhibition of Mv-1 Lu cell proliferation at any dose tested; (2) no band detected by immunoblotting using different polyclonal reagents specific for TGF-β1; and (3) no activity retained on or eluted from an affinity column made of immobilized monoclonal antibody against TGF-β₂. Aliquots of the same preparations retained their full immune inhibitory capacity in vivo throughout the various assays. Thus, we must conclude that the immune regulator we have isolated is different from the TGF-β molecule superfamily. In the light of accumulating evidence for the pivotal role of TGF-β₂ or TGF-β₂-like molecules in the regulation of the maternal immune responses toward the fetus, the description of a new distinct molecular species with immunosuppressive properties may well be of physiologic and clinical relevance.