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Prolonged IFN-γ–producing NKT response induced with α-galactosylceramide–loaded DCs

Nature Immunology volume 3, pages 867874 (2002) | Download Citation

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Abstract

Natural killer T (NKT) lymphocytes mediate a rapid reaction to the glycolipid drug α-galactosylceramide (αGalCer), which triggers release of large amounts of cytokines into the serum within 12 h, starting with interleukin 4 (IL-4). When αGalCer is administered to mice on dendritic cells (DCs) instead, the response is more prolonged (>4 days) and marked by a large expansion in IFN-γ–producing NKT cells as well as greater resistance to metastases of the B16 melanoma. Nevertheless, DCs from mice given free αGalCer are able to induce strong IFN-γ–producing NKT responses when transferred to naïve mice, but not when transferred to αGalCer-treated recipients. In the latter, the NKT cells are anergized and can respond to glycolipid only in the presence of supplemental IL-2. Therefore, when αGalCer is selectively targeted to DCs, mice develop a stronger, more prolonged and effector type of NKT response, but this response can be blocked by the induction of anergy after presentation of αGalCer on other cells.

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  • 26 August 2002

    Acknowledgments were updated with note and PDF was appended with note.

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Acknowledgements

We thank M. Dhodapkar for critical reading of the manuscript. (*see note below)

*Note: In the AOP version of this article some text was incorrect. The acknowledgments should read: We thank S. Sidobre for the preparation of CD1d tetramers and M. Dhodapkar for critical reading of the manuscript. These errors have been corrected in the HTML version and will appear correctly in print. The PDF version available online has been appended.

Author information

Author notes

    • Shin-ichiro Fujii
    •  & Kanako Shimizu

    These authors contributed equally to this work.

Affiliations

  1. Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA.

    • Shin-ichiro Fujii
    • , Kanako Shimizu
    •  & Ralph M. Steinman
  2. La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.

    • Mitchell Kronenberg

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Competing interests

R. M. S. has equity in a company that is developing the use of dendritic cells for clinical applications.

Corresponding author

Correspondence to Ralph M. Steinman.

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DOI

https://doi.org/10.1038/ni827

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