T Cell-Mediated Production of Tumour Necrosis Factor-alpha by Monocytes

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Abstract
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 phytohaemagglutin (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 by 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.