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

S Stoll, H Jonuleit, E Schmitt, G Müller… - European journal of …, 1998 - Wiley Online Library
S Stoll, H Jonuleit, E Schmitt, G Müller, H Yamauchi, M Kurimoto, J Knop, AH Enk
European journal of immunology, 1998Wiley Online Library
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 …
Abstract
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‐γ 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‐γ production and Th1 differentiation in primed T cells.
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