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Laboratory of Immunovirology, Department of Microbiology and Immunology, and Pediatric Research Center, University of Montreal and Sainte-Justine Hospital, Montreal, Quebec, Canada
IL-15 is a recently identified cytokine that belongs to the four
-helix bundle cytokine family and possesses biological activities
similar to those of IL-2. Its ability to induce effectors of NK
activity suggests its involvement in innate immunity. In this study, we
analyzed the effect of different viruses (HSV, EBV, respiratory
syncitial virus, vesicular stomatitis virus, influenza virus, reovirus,
and Sendai virus) on the up-regulation of NK activity in vitro.
Exposure of human PBMC to the these viruses resulted in an immediate
up-regulation of NK activity of PBMC via IL-15 induction; this effect
was abrogated in the presence of mAbs to IL-15. Results of experiments
conducted in parallel using mAbs to IL-15, as well as to other
cytokines (IL-2, IL-12, IFN-
, and TNF-), clearly indicated that
IL-15 was specifically responsible for the observed effect.
Furthermore, supernatants of virus-infected PBMC cultures significantly
enhanced NK activity of uninfected PBMC in vitro. An increase of IL-15
protein levels 20 h postinfection was also confirmed in a bioassay
using the IL-2-dependent cell line CTLL. Kinetic analysis of IL-15 mRNA
expression using a semiquantitative RT-PCR revealed that the level of
IL-15 messages peaked at different time points (up to 12 h)
postinfection, depending on the nature of the virus. Taken together,
these results suggest that the IL-15 response of the host to viral
infection and the subsequent NK cell activation represent an important
effector mechanism of the innate immune surveillance of the host
against viral infections.
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