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

The heterodimeric interferon (IFN)-gamma receptor (IFN-gammaR) is formed of two chains. Here we show that the binding chain (IFN-gamma R1) was highly expressed on the membranes of T, B, and myeloid cells. Conversely, the tran sducing chain (IFN-gamma R2) was highly expressed on the surfaces of myeloi d cells, moderately expressed on B cells, and poorly expressed on the surfa ces of T cells. Differential cell membrane expression of IFN-gamma R2 deter mined the number of receptor complexes that transduced the IFN-gamma signal and resulted in a different response to IFN-gamma. After IFN-gamma stimull ation, high IFN-gamma R2 membrane expression induced rapid activation of si gnal transducer and activator of transcription-1 (STAT-1) and high levels o f interferon regulatory factor-1 (IRF-1), which then triggered the apoptoti c program. By contrast, low cell membrane expression resulted in slow activ ation of STAT-1, lower levels of IRF-1, and induction of proliferation. Bec ause the forced expression of IFN-gamma R2 on T cells switched their respon se to IFN-gamma from proliferative to apoptotic, we concluded that the surf ace expression of IFN-gamma R2 determines whether a cell stimulated by IFN- gamma undergoes proliferation or apoptosis.