Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2000 Jul;1(1):70-6.
doi: 10.1038/76940.

Interferon alpha/beta-mediated inhibition and promotion of interferon gamma: STAT1 resolves a paradox

K B Nguyen  1 , L P Cousens, L A Doughty, G C Pien, J E Durbin, C A Biron
Affiliations

Interferon alpha/beta-mediated inhibition and promotion of interferon gamma: STAT1 resolves a paradox

K B Nguyen et al. Nat Immunol. 2000 Jul.

Abstract

Induction of high systemic levels of type 1 interferons (IFNs) IFN-alpha and IFN-beta is a hallmark of many viral infections. In addition to their potent antiviral effects, these cytokines mediate a number of immunoregulatory functions and can promote IFN-gamma expression in T cells. However, during viral infections of mice IFN-gamma production is not always observed at the same time as systemic IFN-alpha/beta production and when, elicited at these times, is IFN-alpha/beta-independent. We demonstrate that type 1 interferons not only fail to induce, but also act to inhibit, IFN-gamma expression by both NK and T cells. The mechanism of inhibition is dependent upon the IFN-alpha/beta receptor and the signal transducer and activator of transcription 1 (STAT1). In the absence of STAT1, not only are the IFN-alpha/beta-mediated inhibitory effects completely abrogated, but the cytokines themselves can induce IFN-gamma expression. These results indicate that endogenous biochemical pathways are in place to negatively regulate NK and T cell IFN-gamma expression elicited by IFN-alpha/beta or other stimuli, at times of innate responses to viral infections. They also show that type 1 interferon signaling can occur through STAT1-dependent and independent mechanisms and suggest that efficient induction of IFN-gamma expression by IFN-alpha/beta requires STAT1 regulation. Such immunoregulatory pathways may be critical for shaping the endogenous innate and virus-specific adaptive immune responses to viral infections.

PubMed Disclaimer

Comment in

  • Type 1 IFNs in human versus mouse.
    Buclin T, Spertini F. Buclin T, et al. Nat Immunol. 2000 Oct;1(4):265. doi: 10.1038/79701. Nat Immunol. 2000. PMID: 11017090 No abstract available.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types