Down-regulation of human tumor necrosis factor-β gene expression by cells with suppressive activity

Doron Aframian, Mark Katzenellenbogen, Gila Arad, Farhat Osman, Dror Sayar, Mali Ketzinel, Elimelech Deutsch, Raymond Kaempfer*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    4 Scopus citations


    Human TNF-β (lymphotoxin) gene expression is down-regulated by immunosuppression. Induction of TNF-β mRNA in lymphoid cells is greatly enhanced by γ-irradiation, cyclophosphamide and cimetidine, agents that each inhibit activation of suppressive cells. The level of TNF-β mRNA expressed in response to stimulation, whether by mitogen or antigen, is reduced strongly by concomitant activation of suppressive cell subsets. Removal of CD8 or CD11b cells leads to a pronounced superinduction of TNF-β mRNA in the depleted cell population. Induction of TNF-β mRNA precedes appearance of suppressive cell activity, allowing for temporary expression. The TNF-β gene is as sensitive as IFN-γ and IL-2 genes to suppression. Hence, three genes characteristically expressed in Th1 cells, encoding IL-2, IFN-γ, and TNF-β, are similarly regulated by cell-mediated suppression. Actual levels of TNF-β during an immune response are determined by the balance between activities of expressing and suppressing cell subsets, both transiently manifested.

    Original languageAmerican English
    Pages (from-to)171-176
    Number of pages6
    JournalImmunology Letters
    Issue number2-3
    StatePublished - 2 Dec 1996


    • CD11b cells
    • CD8 cells
    • human tumor necrosis factor-β gene regulation
    • immunosuppression


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