Cytokine expression by murine DX5+ cells in response to IL-12, IL-18, or the combination of IL-12 and IL-18.
In this study we analyzed the response of DX5+ NK and NK T cells to in vitro stimulation with IL-12 or IL-18. Production of IFN-gamma in response to either IL-12 or IL-18 was dependent upon costimulation with either IL-2 or IL-15. DX5+ splenocytes showed a rapid (6 h) and sustained (6-72 h) accumulation of IFN-gamma transcripts followed by a delayed (12-24 h) up-regulation of IL-10 or IL-13 expression in response to IL-2 + IL-12 or IL-2 + IL-18, respectively. Incubation of DX5+ splenocytes with the combination of IL-2 + IL-12 + IL-18 resulted in up-regulation of IFN-gamma and IL-13 transcripts but down-regulation of IL-10 expression. Furthermore, two distinct populations of cells producing differing amounts of IFN-gamma were observed by intracellular staining after stimulation with IL-2 + IL-12 + IL-18. Last, we demonstrate that DX5+ cells respond to IL-18 independently of IL-12, as cells from both wild-type and IL-12Rbeta2KO mice produce IFN-gamma and IL-13 in response to IL-2 + IL-18.
Chakir
H
H
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada, K1H 8M5. jwebb@uottawa.ca
Lemay
A M
AM
Webb
J R
JR
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004347:Drug Interactions; D018664:Interleukin-12 / Q000276:immunology* / Q000494:pharmacology; D020382:Interleukin-18 / Q000276:immunology* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D020382:Interleukin-18; D018664:Interleukin-12