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Natural killer-like nonspecific tumor cell lysis mediated by specific ligand-activated Valpha14 NKT cells

T Kawano1, J Cui, Y Koezuka

  • 1Core Research for Evolutional Science and Technology Project, Japan Science and Technology Corporation and Division of Molecular Immunology, Center for Biomedical Science, School of Medicine, Chiba University, 1-8-1 Inohana, Chuo, Chiba 260-8670, Japan.

Proceedings of the National Academy of Sciences of the United States of America
|May 20, 1998
PubMed

Insights

Alpha-galactosylceramide (alpha-GalCer) activates Valpha14 NKT cells, preventing tumor metastasis. These activated cells utilize a natural killer (NK)-like mechanism for direct tumor cell killing, independent of CD1d/T cell receptor interactions.

Area of Science:

  • Immunology
  • Cancer Research
  • Cell Biology

Background:

  • A novel lymphocyte subset, Valpha14 NKT cells, expresses a unique T cell receptor.
  • Alpha-galactosylceramide (alpha-GalCer) is identified as a specific ligand for this T cell receptor.

Purpose of the Study:

  • To investigate the anti-tumor effects of alpha-GalCer.
  • To elucidate the effector mechanisms employed by alpha-GalCer-activated Valpha14 NKT cells.

Main Methods:

  • Administration of alpha-GalCer to Valpha14 NKT cells.
  • Assessment of tumor metastasis prevention.
  • Analysis of cytotoxic mechanisms using cold target inhibition and concanamycin A treatment.
  • Evaluation of antibody-mediated blockade of various cell surface molecules.

Main Results:

  • Alpha-galactosylceramide selectively activates Valpha14 NKT cells.
  • Activated Valpha14 NKT cells effectively prevent tumor metastasis.
  • The cytotoxic activity relies on perforin secretion, characteristic of NK-like cytotoxicity.
  • Cytotoxicity is independent of CD1d, Vbeta8, NK1.1, Ly49C, Fas, or Fas ligand.

Conclusions:

  • Ligand-activated Valpha14 NKT cells exhibit potent anti-metastatic properties.
  • These cells mediate tumor cell killing through a CD1d/T cell receptor-independent, NK-like mechanism involving perforin.

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