The Journal of Experimental Medicine
Aegean Conferences: 2009 Conferences
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Published 21 July 2003. doi:10.1084/jem.20030324
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© Rockefeller University Press, 0022-1007/2003/7/267 $5.00
The Journal of Experimental Medicine, Volume 198, Number 2, 267-279

Activation of Natural Killer T Cells by {alpha}-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, Kanako Shimizu, Caroline Smith, Laura Bonifaz and 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: steinma{at}mail.rockefeller.edu

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 {alpha}-galactosylceramide ({alpha}GalCer) 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)-{gamma} production, and stimulation of the mixed leukocyte reaction. These changes were not induced directly by {alpha}GalCer 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 {alpha}GalCer, mice were given {alpha}GalCer 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-{gamma} producing, CD4+ and CD8+ T cells upon transfer into naive animals. In the latter instance, immune priming did not require further exposure to ovalbumin, {alpha}GalCer, NKT, or NK cells. Therefore a single dose of {alpha}GalCer 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.

Key Words: {alpha}-galactosylceramide • dendritic cell maturation • dendritic cells • exogenous pathway • T cell–mediated immunity


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