Interferon γ (IFN-γ) responsiveness in certain cells depends on the state of cellular differentiation or activation. Here an in vitro developmental system was used to show that IFN-γ produced during generation of the CD4+ T helper cell type 1 (TH1) subset extinguishes expression of the cells (Fig. 3A). None of these genes guishes expression of the IFN-γ receptor β subunit, resulting in T H1 cells that are unresponsive to IFN-γ. This β chain loss also occurred in IFN-yγ-treated TH2 cells and thus represents a specific response of CD4+ T cells to IFN-γ rather than a TH1-specific Differentiation event. These results differentiation event. These results define a mechanism of cellular desensitization where a cytokine down-regulates expression of a receptor subunit required primarily for sigmammalian Ras can substitute for yeast Ras naling and not ligand binding.