First Author | Yang J | Year | 1999 |
Journal | Eur J Immunol | Volume | 29 |
Issue | 2 | Pages | 548-55 |
PubMed ID | 10064070 | Mgi Jnum | J:332070 |
Mgi Id | MGI:7408007 | Doi | 10.1002/(SICI)1521-4141(199902)29:02<548::AID-IMMU548>3.0.CO;2-Z |
Citation | Yang J, et al. (1999) Induction of interferon-gamma production in Th1 CD4+ T cells: evidence for two distinct pathways for promoter activation. Eur J Immunol 29(2):548-55 |
abstractText | IFN-gamma produced by CD4+ T helper 1 (Th1) cells promotes protection against intracellular pathogens. Antigen activation of Th1 cells is an important mode of IFN-gamma induction, but here we analyze a second, antigen-nonspecific pathway capable of inducing full IFN-gamma transcription. IL-12 or IL-18 alone do not induce IFN-gamma mRNA, and only modestly augment antigen-induced IFN-gamma mRNA from Th1 cells. However, IL-12 and IL-18 together fully induce IFN-gamma transcription independently of TCR-activated signals, by a mechanism that does not simply involve Stat4 and NF-kappaB activation, but requires additional protein synthesis. Cyclosporin A inhibits TCR-induced IFN-gamma production, but not IL-12/IL-18-induced IFN-gamma production, biochemically discriminating between these pathways. These results suggest that the two pathways induce IFN-gamma production through functionally segregated but spatially overlapping cis-acting elements, similar to other genes under the control of two or more promoters. |