Contrasting effect of alpha/beta- and gamma-interferons on expression of macrophage Ia antigens

Abstract

IFN-gamma is known to induce the expression of Ia antigens on macrophages. We found that murine IFN-alpha and -beta blocked the effects of IFN-gamma in a dose-dependent manner. The antagonistic effect of IFN-alpha and -beta was observed even when macrophages were prestimulated with IFN-gamma. These inhibitory effects of IFN-alpha or -beta were blocked by their respective antibodies. The block exerted by IFN-alpha/beta was similar whether Ia levels were monitored by immunofluorescence with anti-Ia mAb, or by stimulation of freshly sensitized, alloreactive T lymphoblasts. Adherent macrophage-rich populations from newborn mice were incapable of expressing Ia antigens following stimulation with IFN-gamma, and would inhibit the response of adult macrophages to this lymphokine. Addition of anti-IFN-beta mAb, but not anti-IFN-alpha allowed newborns' macrophages to express Ia in response to IFN-gamma, and ablated the suppressive activity toward adult cells. These results indicate that IFN-alpha and -beta, which can be produced in the course of self-defense responses and during ontogeny, may contribute to the down-regulation of macrophage Ia expression.