Induction of Ia and H-2 antigens on a macrophage cell line by immune interferon.

Recent work from a number of laboratories has suggested that Ia antigen expression on macrophages can be modulated by soluble factors released by T cells after antigen or mitogen activation. The murine macrophage tumor cell line, WEHI-3, provides an in vitro system for the study of this type of lymphokine regulation of Ia antigen expression. Previous work from our laboratory has shown that supernates from Concanavalin A-activated rat or mouse spleen cells (Con A sup) can stimulate increased levels of biosynthesis and cell surface expression of both Ia and H-2K,D antigens on this cell line. The experiments described in this report were designed to identify the regulatory factor responsible for this inducing activity, and in particular to determine whether the inducing factor present in crude supernatant fluids is immune interferon (IFN-gamma). These experiments show that: 1) murine IFN-gamma, produced free of other lymphokines by recombinant DNA technology and DNA-mediated gene transfer, can induce Ia antigen expression and increase H-2 antigen expression on WEHI-3 cells; 2) the biochemical characteristics of partially purified inducing factor from crude supernate fluids are similar to those previously described for murine IFN-gamma by other investigators; and 3) both crude Con A sup and IFN-gamma-containing supernates have inducing activity and antiviral activity which exhibit very similar dose-related responses. These results support the conclusion that the previously described ability of Con A sup to regulate MHC antigen expression on WEHI-3 cells is due to the activity of immune interferon in those supernates.