International Immunology, Vol. 12, No. 7, 987-994,
July 2000
© 2000 Japanese Society for Immunology
The interface between innate and acquired immunity: glycolipid antigen presentation by CD1d-expressing dendritic cells to NKT cells induces the differentiation of antigen-specific cytotoxic T lymphocytes
1 Division of Immunoregulation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
2 Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation, Tokai University School of Medicine, Bohseidai, Isehara 259-1193, Japan
3 Department of Immunology, Juntendo University School of Medicine, Tokyo 113-0033, Japan
4 Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
5 CREST (Core Research for Evolutional Science and Technology) Project and Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Correspondence to: T. Nishimura, Division of Immunoregulation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
In vivo administration of NKT cell ligand, 
-galactosylceramide (-GalCer), caused the activation of NKT cells to induce a strong NK activity and cytokine production by CD1d-restricted mechanisms. Surprisingly, we also found that -GalCer induced the activation of immunoregulatory cells involved in acquired immunity. Specifically, in vivo administration of -GalCer resulted in the induction of the early activation marker CD69 on CD4+ T cells, CD8+ T cells and B cells in addition to macrophages and NKT cells. However, no significant induction of CD69 was observed on cells from CD1d- or V14 NKT-deficient mice, indicating an essential role for the interaction between NKT cells and CD1d-expressing dendritic cells (DC) in the activation of acquired immunity in response to -GalCer. Indeed, in vivo injection of -GalCer resulted not only in the activation of NKT cells but also in the generation of CD69+CD8+ T cells possessing both cytotoxic T lymphocyte (CTL) activity and IFN-
-producing ability. Tumor-specific CTL generation was also accelerated by -GalCer. The critical role of CD40–CD40 ligand (CD40L)-mediated NKT–DC interaction during the development of CD69+CD8+ CTL by -GalCer was demonstrated by blocking experiments using anti-CD40L mAb. These findings provide direct evidence for a critical role of CD1d-restricted NKT cells and DC in bridging innate and acquired immunity.
Keywords: -galactosylceramide, CD40, CD40 ligand, cytotoxic T lymphocyte, dendritic cell, NKT cells
Transmitting editor: M. Miyasaka
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