LIGAND-INDUCED AUTOREGULATION OF IFN-GAMMA RECEPTOR-BETA CHAIN EXPRESSION IN T-HELPER CELL SUBSETS

Interferon gamma (IFN-gamma) responsiveness in certain cells depends o n the state of cellular differentiation or activation. Here an in vitr o developmental system was used to show that IFN-gamma produced during generation of the CD4(+) T helper cell type 1 (T(H)1) subset extingui shes expression of the IFN-gamma receptor beta subunit, resulting in T (H)1 cells that are unresponsive to IFN-gamma. This beta chain loss al so occurred in IFN-gamma-treated T(H)2 cells and thus represents a spe cific response of CD4(+) T cells to IFN-gamma rather than a T(H)1-spec ific differentiation event. These results define a mechanism of cellul ar desensitization where a cytokine down-regulates expression of a rec eptor subunit required primarily for signaling and not ligand binding.