Suppression of Macrophage Ia Antigen Expression by Endogenous Interferon-α/β

Abstract

Exogenous interferon-α (IFN-α) and interferon-β (IFN-β) (type I IFNs) are known to suppress the IFN-γ-dependent expression of class II MHC (Ia) antigens on macrophages (Mϕ). We report here that the endogenous type I IFNs produced by Mϕ in responser to IFN inducers regulate Ia expression of the Mϕ themselves. Coculture of Mϕ with IFN-γ and polyinosinic-polycytidylic acid [poly(I):poly(C)] resulted in the reduction of Ia expression in comparison with those cultured without poly(I):poly(C). Pretreatment of Mϕ with poly(I):poly(C) or a bacterial lipopolysaccharide (LPS), which is also a potent IFN inducer, in vitro or in vivo, before being exposed to IFN-γ was also effective in suppressing the Ia expression. Such suppression was abolished by the addition of anti-IFN-α/β antibodies to the Mϕ culture along with IFN-γ. Mϕ cultured with L-cell conditioned medium (LCM) containing M-CSF were less capable of expressing Ia antigens than those cultured without LCM. The Ia-expressing ability of LCM-treated Mϕ was also restored by the addition of anti-IFN-α/β antibodies. Mϕ in the early stage of sterile inflammation were less responsive to IFN-γ than those in the late stage. These results suggest that endogenous type I IFNs, which are produced in response to natural or synthetic IFN-inducers, regulate Mϕ Ia expression in an autocrinal manner.