Type I interferons enhance production of IFN-gamma by NK cells.
In murine models, challenge with different viral and parasitic infection is closely associated with the production of type I interferons (IFN-alpha/beta) and NK cell production of interferon-gamma (IFN-gamma). Therefore, we wished to determine if IFN-alpha/beta had a role in the regulation of NK cell production of IFN-gamma. IFN-alpha/beta alone stimulated low levels of IFN-gamma production by purified populations of IL-2 activated NK cells but in combination with IL-12 resulted in the production of significant levels of IFN-gamma. Interestingly, maximal production of IFN-gamma by NK cells stimulated with IL-2 plus IFN-alpha/beta was dependent on endogenous tumor necrosis factor-alpha (TNF-alpha). Further studies revealed that TNF-alpha enhanced the ability of IFN-alpha/beta to stimulate production of IFN-gamma by NK cells. In contrast to the stimulatory effect of IFN-alpha/beta on NK cell production of IFN-gamma, IFN-alpha/beta inhibited IL-2 induced proliferation of NK cells. This inhibitory effect was not reversed by the addition of neutralizing antibodies specific for IFN-gamma or TNF-alpha. These data demonstrate that the type I interferons enhance NK cell production of IFN-gamma and suggest that they may be important in the regulation of NK cell production of IFN-gamma during infection.
Hunter
C A
CA
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6008, USA. chunter@phl.vet.upenn.edu
Gabriel
K E
KE
Radzanowski
T
T
Neyer
L E
LE
Remington
J S
JS
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division; D005260:Female; D007370:Interferon Type I / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000998:Antiviral Agents; D007370:Interferon Type I; D016898:Interferon-alpha; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D007371:Interferon-gamma