Interferon-γ receptor 2 expression as the deciding factor in human T, B, and myeloid cell proliferation or death

Abstract Theheterodimeric interferon (IFN)-γ receptor (IFN-γR) is formed of two chains. Here we show that the binding chain (IFN-γR1) was highly expressed on the membranes of T, B, and myeloid cells. Conversely, the transducing chain (IFN-γR2) was highly expressed on the surfaces of myeloid cells, moderately expressed on B cells, and poorly expressed on the surfaces of T cells. Differential cell membrane expression of IFN-γR2 determined the number of receptor complexes that transduced the IFN-γ signal and resulted in a different response to IFN-γ. After IFN-γ stimulation, high IFN-γR2 membrane expression induced rapid activation of signal transducer and activator of transcription-1 (STAT-1) and high levels of interferon regulatory factor-1 (IRF-1), which then triggered the apoptotic program. By contrast, low cell membrane expression resulted in slow activation of STAT-1, lower levels of IRF-1, and induction of proliferation. Because the forced expression of IFN-γR2 on T cells switched their response to IFN-γ from proliferative to apoptotic, we concluded that the surface expression of IFN-γR2 determines whether a cell stimulated by IFN-γ undergoes proliferation or apoptosis.