T Cell‐mediated Cognate Signaling of Nitric Oxide Production by Macrophages. Requirements for Macrophage Activation by Plasma Membranes Isolated From T Cells

Document Type

Article

Publication Date

1-1-1993

Description

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)‐γ and lipopolysaccharide (LPS). The current study demonstrates that, in the absence of LPS, T lymphocytes can provide cognate signal(s) which synergize with IFN‐γ in stimulating macrophage RNI production, as evidenced by the ability of plasma membranes from T cell clones to activate IFN‐γ‐primed macrophages. Although viable resting T cells can activate IFN‐γ‐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‐γ‐primed macrophages. However, in contrast to the antigen‐specific interaction of macrophages with viable resting T cells, the activation of IFN‐γ‐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‐γ‐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.

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