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 active 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 TH2 and from activated TH1 cells were equally effective in activating IFN-gamma-primed macrophages, suggesting that the dominance of TH1 over TH2 cells in cell-mediated responses involving macrophage effectors 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.
Tao
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Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614-0759.
Stout
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D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology; D005260:Female; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis*; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D009569:Nitric Oxide