TY - JOUR
T1 - Interferon-β mediates stromal cell rescue of T cells from apoptosis
AU - Pilling, Darrell
AU - Akbar, AN
AU - Girdlestone, John
AU - Orteu, CH
AU - Borthwick, NJ
AU - Amft, Esther
AU - Scheel-Toellner, Dagmar
AU - Buckley, Christopher
AU - Salmon, Michael
PY - 1999/3/1
Y1 - 1999/3/1
N2 - 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 G(0)/G(1) 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 T cell survival in a resting G(0)/G(1) state. We now report that interferon-beta is the principal mediator of stromal cell-mediated T cell rescue from apoptosis. Interferon-alpha and -beta promote the reversion of blast T cells to a resting G(0)/G(1) configuration with all the characteristic features of stromal cell rescue; such as high Bcl-X-L 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.
AB - 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 G(0)/G(1) 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 T cell survival in a resting G(0)/G(1) state. We now report that interferon-beta is the principal mediator of stromal cell-mediated T cell rescue from apoptosis. Interferon-alpha and -beta promote the reversion of blast T cells to a resting G(0)/G(1) configuration with all the characteristic features of stromal cell rescue; such as high Bcl-X-L 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.
U2 - 10.1002/(SICI)1521-4141(199903)29:03<1041::AID-IMMU1041>3.0.CO;2-#
DO - 10.1002/(SICI)1521-4141(199903)29:03<1041::AID-IMMU1041>3.0.CO;2-#
M3 - Article
C2 - 10092109
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
VL - 29
SP - 1041
EP - 1050
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 3
ER -