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Blood, 15 January 2004, Vol. 103, No. 2, pp. 648-655.
Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2002-07-2322.
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IMMUNOBIOLOGY
Interleukin-18 attracts plasmacytoid dendritic cells (DC2s) and promotes Th1 induction by DC2s through IL-18 receptor expression
Arthur Kaser,
Susanne Kaser,
Nicole C. Kaneider,
Barbara Enrich,
Christian J. Wiedermann, and
Herbert Tilg
From the Division of Gastroenterology and Hepatology and the Division of General Internal Medicine, Department of Medicine, University Hospital Innsbruck, Innsbruck, Austria.
In vivo evidence suggests that interleukin-18 (IL-18) shapes the development of adaptive immunity toward T-helper cell type 1 (Th1) responses. Monocyte-derived dendritic cells 1 (DC1s) preferentially induce a Th1 response, while plasmacytoid DC-derived DC2s have been linked to a Th2 response. We analyzed the role of IL-18 during the initiation phase of a Th response in vitro to elucidate the basis of these in vivo observations. IL-18 was constitutively released from DC1s, but not DC2s. Neutralization of IL-18 in coculture experiments of DC1s with allogeneic naive T lymphocytes did not alter the Th1/Th2 phenotype, while anti–IL-12 efficiently down-regulated the Th1 response. Unexpectedly, IL-18 receptor (IL-18R)  and  chains were expressed on DC2 lineage. IL-18R expression was functional, as IL-18 induced chemotaxis in plasmacytoid DCs (pre-DC2s) and enhanced the allostimulatory capacity of IL-3–differentiated DC2s. Pre-DC2s exposed to IL-18 skewed the development of Th cells toward Th1 in coculture experiments of DC2s and allogeneic naive T cells, which was inhibited by IL-12 p70 neutralization. IL-18 might have a profound role during the initiation phase of an immune response by recruiting pre-DC2s and modulating the function of DC2s.
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