Interferon‐β 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 γ 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 G0 /G1 state. We now report that interferon‐β is the principal mediator of stromal cell‐mediated T cell rescue from apoptosis. Interferon‐α and ‐β promote the reversion of blast T cells 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.