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 memor y, 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 recep tor promote the survival of T cell blasts, but also induce proliferation. I n contrast, soluble factors secreted by stromal cells induce T cell surviva l in a resting G(0)/G(1) state. We now report that interferon-beta is the p rincipal mediator of stromal cell-mediated T cell rescue from apoptosis. In terferon-alpha and -beta promote the reversion of blast T cells to a restin g G(0)/G(1) configuration with all the characteristic features of stromal c ell rescue; such as high Bcl-X-L expression and low Bcl-2. Type I interfero ns and stromal cells stimulate apparently identical signaling pathways, lea ding to STAT-1 activation. We also show that this mechanism may play a fund amental role in the persistence of T cells at sites of chronic inflammation ; suggesting that chronic inflammation is an aberrant consequence of immuno logical memory.