Functional Characterization of Murine Cell Lines Expressing High, Intermediate, or Negative Levels of Surface Receptors for Interferon-γ

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Abstract
Using radioiodinated murine interferon-γ(IFN-γ), various cell lines were analyzed for their capacity to bind IFN-γ and to respond to its biological activity as measured by activation of the 2′,5′-oligoadenylate (2-5A) synthetase, induction of the antiviral activity, and inhibition of [3H]thymidine uptake. A T-cell lymphoma, EL-4, was found to express relatively high number of specific membrane receptors for IFN-γ (60,000/cell) with a dissociation constant of around 9 x 10-10 M. By contrast, a fibroblast cell line, K-BALB, transformed by the Kirstein murine sarcoma virus, was found negative for binding of radioiodinated IFN-γ, even in the presence of high ligand concentrations. Other cell lines displayed numbers of receptors varying between 650 to 20,000 binding sites/cell with Kd ranging between 5 x 10-9 to 9 x 10-10 M. When incubated with EL-4 expressing high levels of specific receptors, IFN-γ caused stimulation of cell growth, but not resistance to viral (vesicular stomatitis virus) infection and expression of 2-5A synthetase. By contrast, when L1210 and TS/A cells, expressing intermediate levels of specific receptors, were incubated with IFN-γ, inhibition of cell growth, induction of antiviral resistance and activation of 2-5A synthetase was observed. Finally, K-BALB cells, lacking specific receptors for IFN-γ, were completely unsensitive to its biological activity. The present system could represent a useful model for the characterization of the interaction of IFN-γ with target cells at molecular levels.