T-CELL-MEDIATED COGNATE SIGNALING OF NITRIC-OXIDE PRODUCTION BY MACROPHAGES - REQUIREMENTS FOR MACROPHAGE ACTIVATION BY PLASMA-MEMBRANES ISOLATED FROM T-CELLS

Macrophage generation of reactive nitrogen intermediates (RNI) represents a major effector mechanism in anti-microbial immunity and non-septic inflammatory reactions. The induction of macrophage RNI production has been demonstrated to require at least two signals which in microbial infections can be provided by interferon (IFN)-gamma and lipopolysaccharide (LPS). The current study demonstrates that, in the absence of LPS, T lymphocytes can provide cognate signal(s) which synergize with IFN-gamma in stimulating macrophage RNI production, as evidenced by the ability of plasma membranes from T cell clones to activate IFN-gamma-primed macrophages. Although viable resting T cells can activate IFN-gamma-primed macrophages by an interaction that is antigen specific, plasma membranes from resting T cells do not activate macrophages. Plasma membranes from T cells activated by immobilized anti-CD3 were able to effectively induce RNI production in IFN-gamma-primed macrophages. However, in contrast to the antigen-specific interaction of macrophages with viable resting T cells, the activation of IFN-gamma-primed macrophages by membranes from activated T cells does not display antigen specificity. Plasma membranes from activated T helper T(H)2 and from activated T(H)1 cells were equally effective in activating IFN-gamma-primed macrophages, suggesting that the dominance of T(H)1 over T(H)2 cells in cell-mediated responses involving macrophage effecters is not a reflection of differences in their ability to interact with macrophages but rather is a reflection of their different pattern of cytokine production. These results suggest that the T cell-macrophage interaction involves reciprocal activation of both cells - an antigen-specific activation of the T cells which results in the acquisition of T cell membrane components involved in antigen-nonspecific stimulation of the macrophages