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

J Leukoc Biol. 2001 Dec;70(6):950-60.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / immunology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Division / immunology
  • Cells, Cultured
  • DNA-Binding Proteins / immunology
  • Humans
  • Interferon Regulatory Factor-1
  • Interferon-gamma / immunology
  • Myeloid Cells / cytology
  • Myeloid Cells / immunology*
  • Phosphoproteins / immunology
  • Receptors, Interferon / immunology*
  • STAT1 Transcription Factor
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Trans-Activators / immunology

Substances

  • DNA-Binding Proteins
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Phosphoproteins
  • Receptors, Interferon
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Trans-Activators
  • interferon gamma receptor
  • Interferon-gamma