H2-D(d)-mediated upregulation of interleukin-4 production by natural killer T-cell and dendritic cell interaction |
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Authors: | Mizuuchi Kazuomi Yanagawa Yoshiki Iwabuchi Kazuya Namba Kenichi Kitaichi Nobuyoshi Ohno Shigeaki Onoé Kazunori |
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Affiliation: | Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan. |
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Abstract: | Natural killer T (NKT) cells are capable of subserving apparently opposite functions, the interferon-gamma (IFN-gamma)-mediated enhancement of host defence and interleukin-4 (IL-4) -mediated immune regulation. Although dendritic cells (DCs) potently activate NKT cells, DC regulation of the IL-4-IFN-gamma balance via NKT-cell activation is not well characterized. In the present study, we examined the effect of DC treatment with CpG oligodeoxynucleotide (ODN), a Toll-like receptor 9 ligand, on the induction of NKT-cell cytokine production. CpG-ODN-conditioned and alpha-galactosylceramide (alpha-GalCer)-loaded myeloid DCs (CpG-DCs) from BALB/c mice showed enhanced ability to induce NKT-cell production of IL-4, but not IFN-gamma, compared to alpha-GalCer-loaded control DCs (not treated with CpG-ODN). The CpG-DCs expressed significantly higher levels of H2-D(d) than control DCs, and blocking of the H2-D(d) and Ly49 receptor interaction during antigen presentation completely abolished the enhanced ability of the CpG-DCs to induce NKT-cell production of IL-4. These findings demonstrate that DC recognition of the CpG motif leads to induction of enhanced IL-4 production by NKT cells via interaction of the augmented H2-D(d) with Ly49 receptors on NKT cells. |
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Keywords: | cytokines dendritic cells natural killer T cells |
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