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(Journal of Leukocyte Biology. 2001;70:950-960.)
© 2001 by Society for Leukocyte Biology

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

Paola Bernabei*, Eliana M. Coccia3, Laura Rigamonti*, Marita Bosticardo*, Guido Forni*, Sidney Pestka4, Christopher D. Krause4, Angela Battistini3 and Francesco Novelli*

* Department of Clinical and Biological Sciences, University of Turin, I-10043 Orbassano,
{dagger} Centro Ricerche di Medicina Sperimentale, S. Giovanni Battista Hospital, I-10126 Turin, and
{ddagger} Immunology and Virology Laboratories, Istituto Superiore di Sanitá, I-00161 Rome, Italy; and
§ Department of Molecular Genetics and Microbiology, UMDNJ, Piscataway, New Jersey

Correspondence: Francesco Novelli, Dipartimento di Scienze Cliniche e Biologiche, Universitá di Torino, Ospedale S. Luigi Gonzaga, 10043 Orbassano, Italy. E-mail: franco.novelli{at}unito.it

Theheterodimeric interferon (IFN)-{gamma} receptor (IFN-{gamma}R) 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 transducing chain (IFN-{gamma}R2) 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-{gamma}R2 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-{gamma}R2 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-{gamma}R2 on T cells switched their response to IFN-{gamma} from proliferative to apoptotic, we concluded that the surface expression of IFN-{gamma}R2 determines whether a cell stimulated by IFN-{gamma} undergoes proliferation or apoptosis.

Key Words: human • IFN-{gamma} • IFN-{gamma} receptor • signal transduction • apoptosis




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