A MOUSE PLACENTAL IMMUNOREGULATORY FACTOR DIFFERENT FROM TRANSFORMINGGROWTH-FACTOR-BETA

Of the growth-promoting factors, transforming growth factor beta (TGF- beta) has been most clearly shown to act as a potent regulator of infl ammation and immunity, It is highly suppressive for T and B lymphocyte proliferation, cytotoxic T lymphocyte generation, and lymphokine-acti vated killer cell development, as well as natural killer cell activity , Moreover, there is accumulating evidence that TGF-beta also may cont ribute to impaired immune surveillance of tumor development, In previo us work, we isolated and described a 40 kD glycoprotein extracted from mouse placenta, This placental factor (PF) is also a potent immune mo dulator in vivo: it is highly inhibitory of secondary antibody respons es as well as cellular responses, such as local graft-versus-host reac tions, Because placenta has been shown to be a major source of TGF-bet a and several reports have indicated an important role for TGF-beta in the immunosuppressive mechanisms taking place during the course of ma mmalian gestation, we have looked for the presence of TGF-beta in our placental factor preparations, Our results clearly indicate that they do not contain TGF-beta or TGF-beta-like molecules by the following cr iteria: (1) no inhibition of Mv-1 Lu cell proliferation at any dose te sted; (2) no band detected by immunoblotting using different polyclona l reagents specific for TGF-beta(1); and (3) no activity retained on o r eluted from an affinity column made of immobilized monoclonal antibo dy against TGF-beta(2). Aliquots of the same preparations retained the ir full immune inhibitory capacity in vivo throughout the various assa ys, Thus, we must conclude that the immune regulator we have isolated is different from the TGF-beta molecule superfamily, In the light of a ccumulating evidence for the pivotal role of TGF-beta(2) or TGF-beta(2 )-like molecules in the regulation of the maternal immune responses to ward the fetus, the description of a new distinct molecular species wi th immunosuppressive properties may well be of physiologic and clinica l relevance.