Induction of interferon-γ production in Th1 CD4+ T cells: evidence for two distinct pathways for promoter activation

✍ Scribed by Jianfei Yang; Theresa L. Murphy; Wenjun Ouyang; Kenneth M. Murphy

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 199 KB
• Volume: 29
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/(sici)1521-4141(199902)29:02<548::aid-immu548>3.0.co;2-z

✦ Synopsis

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.