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.
|Number of pages||10|
|Journal||European Journal of Immunology|
|Publication status||Published - 1 Mar 1999|