The activation of natural killer (NK) cells, cytotoxic lymphocytes capable of major histocompatibility complex (MHC)-unrestricted killing and early antiviral defense, is temporally related to the increased interferon (IFN)-alpha/beta production that is seen in the viral infection of mice. Type I IFN (IFN-alpha/beta) are expressed in many cell types early after primary viral infection and have been shown to mediate resistance against a variety of viruses. In this study, the role of the transcriptional activator IFN regulatory factor-1 (IRF-1) in murine NK cell activity was assessed. IRF-1-deficient mice displayed a normal frequency of NK marker-positive cells, but exhibited greatly reduced NK cell-mediated cytotoxicity after both virus infection and stimulation with the IFN inducer polyinosinic:polycytidilic acid in vivo. In vitro, cytolytic activity in IRF-1-deficient NK cells remained defective after stimulation with IFN-beta, IL-2, and IL-12. IRF-1-deficient mice were unable to eliminate syngeneic MHC class I-negative tumor cells in vivo, and had a reduced ability to reject parental semi-allogeneic donor cells from the circulation. Thus, IRF-1 is essential for the induction of NK cell-mediated cytotoxicity and for the in vivo effector functions that are mediated by this activity.
The transcription factor interferon regulatory factor-1 is essential for natural killer cell function in vivo.
- Views Icon Views
- PDF LinkPDF
- Share Icon Share
- Tools Icon Tools
- Search Site
G S Duncan, H W Mittrücker, D Kägi, T Matsuyama, T W Mak; The transcription factor interferon regulatory factor-1 is essential for natural killer cell function in vivo.. J Exp Med 1 November 1996; 184 (5): 2043–2048. doi: https://doi.org/10.1084/jem.184.5.2043
Download citation file: