Polarization of Valpha24+ Vbeta11+ natural killer T cells of healthy volunteers and cancer patients using alpha-galactosylceramide-loaded and environmentally instructed dendritic cells

Cancer Res. 2003 Jul 15;63(14):4101-6.

Abstract

CD1d-restricted natural killer T (NKT) cells play important regulatory roles in various immune responses. NKT cell-derived T helper (Th) 1 cytokines are important in the induction of antitumor immune responses in mice. Because the CD1d-restricted Valpha24(+) Vbeta11(+) NKT cell population in cancer patients is decreased both in size and in its capacity to secrete IFN-gamma, therapeutic strategies based on reconstitution of type 1 polarized Valpha24(+) Vbeta11(+) NKT cells merit additional investigation. Here, we report the simultaneous strong expansion and type 1 polarization of human invariant Valpha24(+) Vbeta11(+) NKT cells using alpha-galactosylceramide-loaded type 1 dendritic cells and interleukin 15. Type 1 polarized Valpha24(+) Vbeta11(+) NKT cells produced high levels of IFN-gamma, tumor necrosis factor alpha, and granulocyte macrophage colony-stimulating factor, and induced strong cytotoxicity in Jurkat cells in an alpha-galactosylceramide-dependent manner. Importantly, the cytokine profile of Valpha24(+) Vbeta11(+) NKT cells that were initially expanded under Th2 polarizing conditions could be reversed to a Th1 cytokine profile, indicating the plasticity of the cytokine profile of the human adult Valpha24(+) Vbeta11(+) NKT cell population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / immunology*
  • Cell Polarity / immunology
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology*
  • Female
  • Galactosylceramides / immunology*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / immunology
  • Interleukin-15 / biosynthesis
  • Interleukin-15 / immunology
  • Jurkat Cells
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Male
  • Middle Aged
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Th2 Cells / immunology

Substances

  • Antigens, CD
  • Galactosylceramides
  • Interleukin-15
  • Interleukin-12