TYPE-I INTERFERON INHIBITION OF SUPERANTIGEN STIMULATION - IMPLICATIONS FOR TREATMENT OF SUPERANTIGEN-ASSOCIATED DISEASE

The interferons (IFNs) are a family of secretory glycoproteins possessing potent antiviral, antiproliferative, antimicrobial, and immunomodulatory activities, It has been shown that the IFNs and superantigens have an important effect on the course of certain autoimmune disorders, and thus we have examined the effect of the type I and type II IFNs on superantigen-induced stimulation. The type I IFNs, alpha, beta, and tau, inhibited induction of T cell proliferation by several staphylococcal enterotoxin superantigens; the type II IFN, gamma, was without effect, The type I IFNs inhibited T cell proliferation to the same extent, approximately 50% at 10(3) units of IFN/ml, and in a dose-dependent manner, Consistent with inhibition of proliferation, the type I IFNs also inhibited IL-2 production as well as levels of IL-2 receptor expression. Inhibition was not increased by using the IFNs in combination, suggesting that they inhibited proliferation by the same mechanism, IFNs alpha and beta, but not IFN-tau, were toxic to cells at high concentrations (greater than or equal to 10(4) units/ml), Thus, the mechanism by which type I IFNs inhibit cell proliferation differs from that associated with their toxic effects, A partial reduction of VP-specific superantigen-induced T cell expansion by type I IFNs was also demonstrated using flow cytometry, We recently showed that superantigens play an important role in the reactivation of experimental allergic encephalomyelitis. The potent antiproliferative activities of the type I IFNs strongly suggest the further study of their use as therapies for superantigen-associated diseases, such as multiple sclerosis and other autoimmune disorders, as well as toxic shock syndrome.