DIFFERENTIAL ACTIVATION OF ANTIGEN-STIMULATED SUICIDE AND CYTOKINE PRODUCTION PATHWAYS IN CD4-CELLS IS REGULATED BY THE ANTIGEN-PRESENTING CELL( T)

Stimulation of the TCR of activated, mature T cells by an APC produces a spectrum of functional responses. Most of those responses positivel y promote immunity and inflammation. However, death of the responding T cell, which would limit subsequent inflammation, can also result fro m such stimulation. We compare the Ag threshold necessary to promote i nflammation through cytokine production with the Ag threshold necessar y to limit inflammation through T cell death. These two responses are independently regulated by the APC and this regulation is selective fo r both different APC products and different T cell subsets. The costim ulator B7 selectively decreases the Ag threshold for cytokine producti on in Th1 cells with no effect on the Ag threshold for Th1 death. B7 h as no effect on the Th2 Ag threshold for cytokine production or death. In contrast, IFN-gamma negatively modulates a macrophage product that selectively increases the threshold of Ag necessary to stimulate deat h in Th2 cells, but has no effect on cytokine production by Th2 cells or cytokine production or death of Th1 cells. This selective regulatio n of cytokine production and T cell death may play an important role i n both shaping the quality of a given immune response and in providing a general mechanism forthe regulation of the immune response by limit ing inflammation and through peripheral deletion of inappropriate T ce ll specificities.