Ligand-induced autoregulation of IFN-γ receptor β chain expression in T helper cell subsets

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 (T_H1) 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 T_H2 cells and thus represents a specific response of CD4⁺ T cells to IFN-γ rather than a T_H1-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.