Innate Valpha14(+) natural killer T cells mature dendritic cells, leading to strong adaptive immunity

Immunol Rev. 2007 Dec:220:183-98. doi: 10.1111/j.1600-065X.2007.00561.x.


The observation that the glycolipid alpha-galactosylceramide (alpha-GalCer) is a potent stimulator of natural killer T (NKT) cells has provided an important means for investigating NKT cell biology. alpha-GalCer is presented on CD1d to the invariant NKT receptor, leading to interleukin-12 (IL-12) production by dendritic cells (DCs) and to NK cell activation. We review our research on the tumor-protective properties of alpha-GalCer, particularly the major role played by DCs. We compared administration of alpha-GalCer on mature DCs with soluble glycolipid and found that DCs induced more prolonged interferon-gamma (IFN-gamma) production by NKT cells and better protection against B16 melanoma. Human alpha-GalCer-loaded DCs also expanded NKT cell numbers in cancer patients. alpha-GalCer-activated NKT cells were then found to induce DC maturation in vivo. The maturing DCs produced IL-12, upregulated co-stimulatory molecules, and induced adaptive immunity to captured cellular antigens, including prolonged, combined CD4(+)/CD8(+) T-cell immunity to dying tumor cells. Surprisingly, co-stimulator-poor tumor cells, if directly loaded with alpha-GalCer ('tumor/Gal') and injected intravenously, also induced strong NKT- and NK-cell responses. The latter killed the tumor/Gal, which were subsequently cross presented by CD1d on DCs to elicit DC maturation and prolonged adaptive T-cell immunity, which lasted 6-12 months. These findings help explain tumor protection via alpha-GalCer and urge development of the DC-NKT axis to provide innate and adaptive immunity to human cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cross-Priming
  • Dendritic Cells / immunology*
  • Galactosylceramides / analysis
  • Galactosylceramides / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunity, Cellular
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology*
  • Mice
  • Neoplasms / immunology
  • Neoplasms / prevention & control*
  • T-Lymphocytes / immunology*


  • Galactosylceramides
  • Histocompatibility Antigens Class I
  • alpha-galactosylceramide
  • Interferon-gamma