T cell-mediated production of tumour necrosis factor-alpha by monocytes.
The aim of this study was to examine the tumour necrosis factor (TNF)-alpha production by peripheral blood mononuclear cells activated by mitogens. Considerable amounts of TNF-alpha, ranging from 1.0 to 5.0 ng/ml, were present in the supernatants of cultures of human peripheral blood mononuclear cells (PBMC), stimulated with either the anti-CD3 monoclonal antibody OKT3 or the lectin phytohaemagglutinin (PHA). The amount of TNF-alpha secreted in the supernatant was closely correlated to the degree of T cell proliferation in such cultures, as measured by [3H]TdR incorporation. In the absence of proliferating T cells the mitogens did not induce secretion of TNF-alpha by monocytes. Supernatants of proliferating T cells were shown to induce TNF-alpha production by monocytes. The macrophage-activating factor gamma interferon (IFN-gamma) was also shown to induce, in the absence of endotoxin, TNF-alpha secretion by monocytes in a dose-dependent manner. The induction of TNF-alpha production by supernatants of proliferating T cells could largely be abrogated by passaging the supernatants on an anti-IFN-gamma column before adding them to the monocytes. It is therefore concluded from this study that the production of TNF-alpha by monocytes can be induced by proliferating T cells and that this induction can largely be attributed to the T cell lymphokine IFN-gamma.
D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000502:physiology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000502:physiology*; D011112:Polymyxin B / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011112:Polymyxin B