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  • Title: Immunoregulation and production of tumor necrosis factor alpha by human thymocytes.
    Author: Reem GH, Duggan A, Schleuning M.
    Journal: Cancer Res; 1989 Jul 01; 49(13):3568-73. PubMed ID: 2659163.
    Abstract:
    We have provided evidence that tumor necrosis factor alpha (TNF-alpha) 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 (alpha-chain, Tac antigen) and by the expression of Tac antigen on the cell surface. Our observations suggest that TNF-alpha 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-alpha 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-alpha of thymocytes induced with IL-2 completely. These observations show that TNF-alpha 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-alpha gene and that the expression of this gene is inhibited by cyclosporin A and dexamethasone.
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