The maturation of dendritic cells (DCs) allows these antigen-presenting cells to initiate immunity. We pursued this concept in situ by studying the adjuvant action of α-galactosylceramide (αGalCer) in mice. A single i.v. injection of glycolipid induced the full maturation of splenic DCs, beginning within 4 h. Maturation was manifest by marked increases in costimulator and major histocompatibility complex class II expression, interferon (IFN)-γ production, and stimulation of the mixed leukocyte reaction. These changes were not induced directly by αGalCer but required natural killer T (NKT) cells acting independently of the MyD88 adaptor protein. To establish that DC maturation was responsible for the adjuvant role of αGalCer, mice were given αGalCer together with soluble or cell-associated ovalbumin antigen. Th1 type CD4+ and CD8+ T cell responses developed, and the mice became resistant to challenge with ovalbumin-expressing tumor. DCs from mice given ovalbumin plus adjuvant, but not the non-DCs, stimulated ovalbumin-specific proliferative responses and importantly, induced antigen-specific, IFN-γ producing, CD4+ and CD8+ T cells upon transfer into naive animals. In the latter instance, immune priming did not require further exposure to ovalbumin, αGalCer, NKT, or NK cells. Therefore a single dose of αGalCer i.v. rapidly stimulates the full maturation of DCs in situ, and this accounts for the induction of combined Th1 CD4+ and CD8+ T cell immunity to a coadministered protein.
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21 July 2003
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July 21 2003
Activation of Natural Killer T Cells by α-Galactosylceramide Rapidly Induces the Full Maturation of Dendritic Cells In Vivo and Thereby Acts as an Adjuvant for Combined CD4 and CD8 T Cell Immunity to a Coadministered Protein
Shin-ichiro Fujii,
Shin-ichiro Fujii
Laboratory of Cellular Physiology and Immunology and the Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
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Kanako Shimizu,
Kanako Shimizu
Laboratory of Cellular Physiology and Immunology and the Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
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Caroline Smith,
Caroline Smith
Laboratory of Cellular Physiology and Immunology and the Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
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Laura Bonifaz,
Laura Bonifaz
Laboratory of Cellular Physiology and Immunology and the Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
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Ralph M. Steinman
Ralph M. Steinman
Laboratory of Cellular Physiology and Immunology and the Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
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Shin-ichiro Fujii
Laboratory of Cellular Physiology and Immunology and the Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
Kanako Shimizu
Laboratory of Cellular Physiology and Immunology and the Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
Caroline Smith
Laboratory of Cellular Physiology and Immunology and the Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
Laura Bonifaz
Laboratory of Cellular Physiology and Immunology and the Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
Ralph M. Steinman
Laboratory of Cellular Physiology and Immunology and the Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
Address correspondence to Ralph M. Steinman, Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021-6399. Phone: 212-327-8106; Fax: 212-327-8875; E-mail: [email protected]
*
Abbreviations used in this paper: TLR, Toll-like receptor; MLR, mixed leukocyte reaction; αGalCer, α-galactosylceramide.
Received:
March 03 2003
Revision Received:
April 30 2003
Accepted:
April 30 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 198 (2): 267–279.
Article history
Received:
March 03 2003
Revision Received:
April 30 2003
Accepted:
April 30 2003
Citation
Shin-ichiro Fujii, Kanako Shimizu, Caroline Smith, Laura Bonifaz, Ralph M. Steinman; Activation of Natural Killer T Cells by α-Galactosylceramide Rapidly Induces the Full Maturation of Dendritic Cells In Vivo and Thereby Acts as an Adjuvant for Combined CD4 and CD8 T Cell Immunity to a Coadministered Protein . J Exp Med 21 July 2003; 198 (2): 267–279. doi: https://doi.org/10.1084/jem.20030324
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