TY - JOUR
T1 - Down-regulation of human tumor necrosis factor-β gene expression by cells with suppressive activity
AU - Aframian, Doron
AU - Katzenellenbogen, Mark
AU - Arad, Gila
AU - Osman, Farhat
AU - Sayar, Dror
AU - Ketzinel, Mali
AU - Deutsch, Elimelech
AU - Kaempfer, Raymond
PY - 1996/12/2
Y1 - 1996/12/2
N2 - 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.
AB - 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.
KW - CD11b cells
KW - CD8 cells
KW - human tumor necrosis factor-β gene regulation
KW - immunosuppression
UR - http://www.scopus.com/inward/record.url?scp=0030566723&partnerID=8YFLogxK
U2 - 10.1016/S0165-2478(96)02668-5
DO - 10.1016/S0165-2478(96)02668-5
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C2 - 9052873
AN - SCOPUS:0030566723
SN - 0165-2478
VL - 54
SP - 171
EP - 176
JO - Immunology Letters
JF - Immunology Letters
IS - 2-3
ER -