Production of functional IL-18 by different subtypes of murine and human dendritic cells (DC): DC-derived IL-18 enhances IL-12-dependent Th1 development.
IL-18 is a recently described cytokine that shares biological activities with IL-12 in driving the development of Th1-type T cells. As dendritic cells (DC) are very potent inducers of T cell proliferation and differentiation we wondered whether they utilize IL-18 as a factor driving Th1 development. We demonstrate by Northern blot and reverse transcription-PCR that various subtypes of human and murine DC as well as the DC-line XS contain IL-18 mRNA. When supernatants of either enriched Langerhans cells (LC) or bone marrow-derived DC were analyzed for production of IL-18 protein, IL-18 production was detected in an IL-18-specific ELISA. To assess whether the IL-18 protein released by DC is functional, we performed a sensitive bioassay using the IL-18-dependent stimulation of concanavalin A-stimulated T cells. Both, supernatants from bone marrow-derived DC and enriched LC induced IFN-gamma production in the T cells. This production was partially inhibitable by addition of anti-IL-18 antiserum. In a TCR-transgenic mouse system we further demonstrate that DC-derived IL-18 potentiates IL-12-dependent Th1 development. Using DC derived from IL-12 knockout animals, we show that DC-derived IL-18 by itself is not capable of inducing Th1 cell differentiation. Together the data demonstrate that subtypes of DC are able to release functional IL-18 that is able to induce IFN-gamma production and Th1 differentiation in primed T cells.
Stoll
S
S
Department of Dermatology, University of Mainz, Germany.
Jonuleit
H
H
Schmitt
E
E
Müller
G
G
Yamauchi
H
H
Kurimoto
M
M
Knop
J
J
Enk
A H
AH
D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation; D002460:Cell Line; D003470:Culture Media; D003713:Dendritic Cells / Q000378:metabolism*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism*; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D007801:Langerhans Cells / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger; D018417:Th1 Cells / Q000378:metabolism*
D003470:Culture Media; D020382:Interleukin-18; D012333:RNA, Messenger; D018664:Interleukin-12