The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20070458
The Journal of Experimental Medicine, Vol. 204, No. 11, 2641-2653
The Rockefeller University Press, 0022-1007 $30.00
© Shimizu et al.
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ARTICLE

 Cross-presentation of glycolipid from tumor cells loaded with {alpha}-galactosylceramide leads to potent and long-lived T cell–mediated immunity via dendritic cells

Kanako Shimizu1, Yuri Kurosawa1, Masaru Taniguchi2, Ralph M. Steinman3, and Shin-ichiro Fujii1

1 Research Unit for Cellular Immunotherapy and 2 Laboratory for Immune regulation, Research Center for Allergy and Immunology, Institute of Physical and Chemical Research, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan
3 Laboratory of Cellular Physiology and Immunology and Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10065

CORRESPONDENCE Shin-ichiro Fujii: fujiis{at}rcai.riken.jp

We report a mechanism to induce combined and long-lived CD4+ and CD8+ T cell immunity to several mouse tumors. Surprisingly, the initial source of antigen is a single low dose of tumor cells loaded with {alpha}-galactosylceramide ({alpha}-GalCer) glycolipid (tumor/Gal) but lacking co-stimulatory molecules. After tumor/Gal injection intravenously (i.v.), innate NKT and NK cells reject the tumor cells, some of which are taken up by dendritic cells (DCs). The DCs in turn cross-present glycolipid on CD1d molecules to NKT cells and undergo maturation. For B16 melanoma cells loaded with {alpha}-GalCer (B16/Gal), interferon {gamma}–producing CD8+ T cells develop toward several melanoma peptides, again after a single low i.v. dose of B16/Gal. In all four poorly immunogenic tumors tested, a single dose of tumor/Gal i.v. allows mice to become resistant to tumors given subcutaneously. Resistance requires CD4+ and CD8+ cells, as well as DCs, and persists for 6–12 mo. Therefore, several immunogenic features of DCs are engaged by the CD1d-mediated cross-presentation of glycolipid-loaded tumor cells, leading to particularly strong and long-lived adaptive immunity.

Abbreviations used: {alpha}-GalCer, {alpha}-galactosylceramide; B16/Gal, B16 melanoma cells loaded with {alpha}-GalCer; DC/Gal, DCs loaded with {alpha}-GalCer; DCT, dopachrome tautomerase; DTR, diphtheria toxin receptor; MNC, mononuclear cell; TAP, transporter associated with antigen presentation; TRP-2, tyrosinase-related protein 2; tumor/Gal, tumor cells loaded with {alpha}-GalCer.


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