A first or dominant immunization. II. Induced immunoglobulin carries transforming growth factor β and suppresses cytolytic T cell responses to unrelated alloantigens

Abstract

Fresh sera from mice immunized by bearing an immunogenic tumor or by repeated injections of allogeneic spleen cells or xenogeneic erythrocytes powerfully suppress cytolytic T cell responses in one-way mixed lymphocyte cultures. Suppression is not antigen specific, though is mediated by immunoglobulin (Ig)G specific for the immunizing antigen. Suppression caused by IgG mimics that caused by active transforming growth factor β (TGF-β). IgG associates with or carries latent TGF-β; however, suppression caused by the complex of IgG-TGF-β requires macrophages (Mφ), whereas active TGF-β alone does not. Also, IgG dissociated from TGF-β does not cause suppression, suggesting that Mφ may take up Ig-TGF-β, process the complex, and deliver active TGF-β to lymphocytes. Indeed, suppression by immune serum was prevented by antibody to Fc receptors, by saturating Fc receptors with heterologous IgGs, and by antibodies against TGF-β. The overall findings reveal a previously unrecognized regulatory circuit whereby IgG produced in response to one antigen nonspecifically downregulates cytolytic T lymphocyte responses to unrelated antigens The findings introduce the intriguing possibility that TGF-β delivered by IgG and processed by Mφ may mediate important biological effects in processes such as wound healing, tumor growth, and some autoimmune diseases.