Activation of a suppressor T-cell pathway by interferon

Abstract

In addition to antiviral activities, murine fibroblast (type I) interferon (IFN-beta) suppresses immune responses. The mechanism(s) by which IFN-beta suppresses antibody responses by murine spleen cells to sheep erythrocytes in vitro has been investigated. IFN-beta-mediated suppression is partially or completely prevented by catalase, 2-mercaptoethanol, and certain peroxidase substrates (ascorbic acid, potassium iodide, and tyrosine). These same reagents also block suppression by mediators from concanavalin A-activated murine suppressor T cells, soluble immune response suppressor (SIRS)/macrophage-derived suppressor factor (Mphi-SF), and act by inactivating Mphi-SF or preventing formation of Mphi-SF from SIRS. Therefore, these experiments suggested that IFN-beta may act by inducing production of a molecule that has properties of SIRS. Treatment of spleen cells with IFN-beta leads to generation of a population of Lyt2+ suppressor T cells that acts by elaborating a soluble factor. This IFN-beta-induced suppressor T-cell factor (IFN-TsF) has properties in common with SIRS. First, both SIRS and IFN-TsF suppress antibody responses with the same characteristic kinetic pattern; responses initiate normally but prematurely terminate after day 4 of culture. Second, IFN-TsF and SIRS are of comparable size (45,000-55,000 daltons) and are converted to Mphi-SF by low (1 microM) concentrations of H2O2 or by macrophages. Third, Mphi-SF obtained from IFN-TsF or SIRS is inactivated by similar concentrations of reagents such as ascorbic acid, potassium iodide, and 2-mercaptoethanol. These data show that the immunosuppressive properties of IFN-beta are due, at least in part, to its ability to activate suppressor T cells that produce mediators that appear to be analogous to those in the SIRS/Mphi-SF pathway of immunosuppression.