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

Eur J Immunol. 1998 Oct;28(10):3231-9. doi: 10.1002/(SICI)1521-4141(199810)28:10<3231::AID-IMMU3231>3.0.CO;2-Q.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Differentiation
  • Cell Line
  • Culture Media
  • Dendritic Cells / metabolism*
  • Humans
  • Interleukin-12 / metabolism*
  • Interleukin-18 / biosynthesis*
  • Interleukin-18 / genetics
  • Langerhans Cells / metabolism
  • Mice
  • Mice, Transgenic
  • RNA, Messenger
  • Th1 Cells / metabolism*


  • Culture Media
  • Interleukin-18
  • RNA, Messenger
  • Interleukin-12