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.
- CD11b cells
- CD8 cells
- human tumor necrosis factor-β gene regulation