TY - JOUR
T1 - Induction of interferon-γ production in Th1 CD4+ T cells
T2 - Evidence for two distinct pathways for promoter activation
AU - Yang, Jianfei
AU - Murphy, Theresa L.
AU - Ouyang, Wenjun
AU - Murphy, Kenneth M.
PY - 1999
Y1 - 1999
N2 - IFN-γ produced by CD4+ T helper 1 (Th1) cells promotes protection against intracellular pathogens. Antigen activation of Th1 cells is an important mode of IFN-γ induction, but here we analyze a second, antigen-nonspecific pathway capable of inducing full IFN-γ transcription. IL-12 or IL-18 alone do not induce IFN-γ mRNA, and only modestly augment antigen-induced IFN-γ mRNA from Th1 cells. However, IL-12 and IL-18 together fully induce IFN-γ transcription independently of TCR-activated signals, by a mechanism that does not simply involve Stat4 and NF-κB activation, but requires additional protein synthesis. Cyclosporin A inhibits TCR-induced IFN-γ production, but not IL-12/IL-18-induced IFN-γ production, biochemically discriminating between these pathways. These results suggest that the two path ways induce IFN-γ production through functionally segregated but spatially overlapping cis-acting elements, similar to other genes under the control of two or more promoters.
AB - IFN-γ produced by CD4+ T helper 1 (Th1) cells promotes protection against intracellular pathogens. Antigen activation of Th1 cells is an important mode of IFN-γ induction, but here we analyze a second, antigen-nonspecific pathway capable of inducing full IFN-γ transcription. IL-12 or IL-18 alone do not induce IFN-γ mRNA, and only modestly augment antigen-induced IFN-γ mRNA from Th1 cells. However, IL-12 and IL-18 together fully induce IFN-γ transcription independently of TCR-activated signals, by a mechanism that does not simply involve Stat4 and NF-κB activation, but requires additional protein synthesis. Cyclosporin A inhibits TCR-induced IFN-γ production, but not IL-12/IL-18-induced IFN-γ production, biochemically discriminating between these pathways. These results suggest that the two path ways induce IFN-γ production through functionally segregated but spatially overlapping cis-acting elements, similar to other genes under the control of two or more promoters.
KW - Cytokine
KW - IFN-γ
KW - IL-12
KW - IL-18
KW - Th1
UR - http://www.scopus.com/inward/record.url?scp=0033033469&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1521-4141(199902)29:02<548::AID-IMMU548>3.0.CO;2-Z
DO - 10.1002/(SICI)1521-4141(199902)29:02<548::AID-IMMU548>3.0.CO;2-Z
M3 - Article
C2 - 10064070
AN - SCOPUS:0033033469
SN - 0014-2980
VL - 29
SP - 548
EP - 555
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 2
ER -