Interferon-beta mediates stromal cell rescue of T cells from apoptosis

Eur J Immunol. 1999 Mar;29(3):1041-50. doi: 10.1002/(SICI)1521-4141(199903)29:03<1041::AID-IMMU1041>3.0.CO;2-#.


The resolution of immune responses is characterized by extensive apoptosis of activated T cells. However, to generate and maintain immunological memory, some antigen-specific T cells must survive and revert to a resting G0/G1 state. Cytokines that bind to the common gamma chain of the IL-2 receptor promote the survival of T cell blasts, but also induce proliferation. In contrast, soluble factors secreted by stromal cells induce Tcell survival in a resting G0/G1 state. We now report that interferon-beta is the principal mediator of stromal cell-mediated Tcell rescue from apoptosis. Interferon-alpha and -beta promote the reversion of blast Tcells to a resting G0/G1 configuration with all the characteristic features of stromal cell rescue; such as high Bcl-XL expression and low Bcl-2. Type I interferons and stromal cells stimulate apparently identical signaling pathways, leading to STAT-1 activation. We also show that this mechanism may play a fundamental role in the persistence of T cells at sites of chronic inflammation; suggesting that chronic inflammation is an aberrant consequence of immunological memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Arthritis, Rheumatoid / immunology
  • DNA-Binding Proteins / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Humans
  • Immunophenotyping
  • Interferon-alpha / immunology
  • Interferon-alpha / pharmacology
  • Interferon-beta / biosynthesis
  • Interferon-beta / immunology*
  • Interferon-beta / pharmacology
  • Milk Proteins*
  • STAT1 Transcription Factor
  • STAT5 Transcription Factor
  • Signal Transduction / immunology
  • Stromal Cells / cytology
  • Stromal Cells / drug effects
  • Stromal Cells / immunology*
  • Synovial Fluid / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Trans-Activators / metabolism


  • DNA-Binding Proteins
  • Interferon-alpha
  • Milk Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT5 Transcription Factor
  • Trans-Activators
  • Interferon-beta