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-gammaR1) was highly expressed on the membranes of T, B, and myeloid cells. Conversely, the transducing chain (IFN-gammaR2) 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-gammaR2 determined the number of receptor complexes that transduced the IFN-gamma signal and resulted in a different response to IFN-gamma. After IFN-gamma stimulation, high IFN-gammaR2 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-gammaR2 on T cells switched their response to IFN-gamma from proliferative to apoptotic, we concluded that the surface expression of IFN-gammaR2 determines whether a cell stimulated by IFN-gamma undergoes proliferation or apoptosis.
Bernabei
P
P
Department of Clinical and Biological Sciences, University of Turin, I-10043 Orbassano, Centro Ricerche di Medicina Sperimentale, S. Giovanni Battista Hospital, I-10126 Turin, Italy.
Coccia
E M
EM
Rigamonti
L
L
Bosticardo
M
M
Forni
G
G
Pestka
S
S
Krause
C D
CD
Battistini
A
A
Novelli
F
F
D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000276:immunology; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000276:immunology; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology; D017471:Receptors, Interferon / Q000276:immunology*; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology; D000096743:Interferon gamma Receptor
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma; D010750:Phosphoproteins; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C494257:IRF1 protein, human; C494079:STAT1 protein, human