We have provided evidence that tumor necrosis factor α (TNF-α) enhances the proliferation and the state of activation of human thymocytes cultured with concanavalin A or interleukin 2 (IL-2), as evidenced by an increase in the expression of the c-myc gene and the gene of the IL-2 receptor (α-chain, Tac antigen) and by the expression of Tac antigen on the cell surface. Our observations suggest that TNF-α interacts with IL-2 and with another factor(s) which is induced in the course of activation by concanavalin A, since the immunosuppressant drug cyclosporin A-, which inhibits thymocyte activation, prevents the effect of TNF-α on thymocytes activated with concanavalin A, whereas anti-Tac, which prevents the binding of IL-2 to its receptor without affecting the production of IL-2 or the expression of IL-2-specific mRNA, inhibits proliferation only partially. By contrast, anti-Tac inhibits the response to TNF-α of thymocytes induced with IL-2 completely. These observations show that TNF-α exerts a potentially important immunoregulatory effect in synergy with IL-2 on thymocytes, which could contribute to tumor rejection. In addition, we show that activated human thymocytes express the TNF-α gene and that the expression of this gene is inhibited by cyclosporin A and dexamethasone.

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This work was supported by NIH Grant RO 1 CA 33653.

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