The antagonistic effect of interferon-beta on the interferon-gamma-induced expression of HLA-DR antigen in a squamous cell carcinoma line.

We examined the effect of type I interferon (IFN) on IFN-gamma-induced HLA-DR antigen expression in A431 cells, a human squamous cell carcinoma line. A431 cells expressed HLA-DR antigen when stimulated with IFN-gamma, but not with IFN-beta. Simultaneous addition of IFN-gamma and IFN-beta to A431 cells resulted in significantly decreased HLA-DR antigen expression when compared to treatment with IFN-gamma alone. Kinetic studies revealed that IFN-beta was required concomitantly or prior to stimulation with IFN-gamma in order to down-regulate expression of HLA-DR antigens. IFN-alpha also inhibited IFN-gamma-induced HLA-DR antigen expression in A431 cells. Analysis of cytoplasmic mRNA showed that simultaneous treatment of A431 cells with IFN-gamma and IFN-beta resulted in a marked decrease of the level of DR alpha specific mRNA when compared to a level reached after treatment with IFN-gamma alone. These results suggest that type I IFN antagonize the IFN-gamma-induced HLA-DR antigen expression in human keratinocyte system, and that this antagonistic effect of type I IFN is confirmed as evidenced by a change in HLA-DR mRNA levels.