Down-regulation of human tumor necrosis factor-beta gene expression by cells with suppressive activity.
Human TNF-beta (lymphotoxin) gene expression is down-regulated by immunosuppression. Induction of TNF-beta mRNA in lymphoid cells is greatly enhanced by gamma-irradiation, cyclophosphamide and cimetidine, agents that each inhibit activation of suppressive cells. The level of TNF-beta 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-beta mRNA in the depleted cell population. Induction of TNF-beta mRNA precedes appearance of suppressive cell activity, allowing for temporary expression. The TNF-beta gene is as sensitive as IFN-gamma and IL-2 genes to suppression. Hence, three genes characteristically expressed in Th1 cells, encoding IL-2, IFN-gamma, and TNF-beta, are similarly regulated by cell-mediated suppression. Actual levels of TNF-beta during an immune response are determined by the balance between activities of expressing and suppressing cell subsets, both transiently manifested.
Aframian
D
D
Department of Molecular Virology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Katzenellenbogen
M
M
Arad
G
G
Osman
F
F
Sayar
D
D
Ketzinel
M
M
Deutsch
E
E
Kaempfer
R
R
D016827:CD8 Antigens / Q000276:immunology; D002478:Cells, Cultured; D002927:Cimetidine / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D015536:Down-Regulation; D005720:Gamma Rays; D005786:Gene Expression Regulation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008233:Lymphotoxin-alpha / Q000235:genetics*; D016177:Macrophage-1 Antigen / Q000276:immunology
D016827:CD8 Antigens; D007166:Immunosuppressive Agents; D008233:Lymphotoxin-alpha; D016177:Macrophage-1 Antigen; D002927:Cimetidine; D003520:Cyclophosphamide