Interferon-beta mediates stromal cell rescue of T cells from apoptosis.
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.
Pilling
D
D
MCR Centre for Immune Regulation, The University of Birmingham, GB.
Akbar
A N
AN
Girdlestone
J
J
Orteu
C H
CH
Borthwick
N J
NJ
Amft
N
N
Scheel-Toellner
D
D
Buckley
C D
CD
Salmon
M
M
D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D008894:Milk Proteins; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D008894:Milk Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D016899:Interferon-beta