Dendritic cells are targets for human invariant Vα24+ natural killer T-cell cytotoxic activity. An important immune regulatory function

Andrew Nicol, Mie Nieda, Yasuhiko Koezuka, Steven Porcelli, Kenji Suzuki, Kenji Tadokoro, Simon Durrant, Takeo Juji

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Objective. Human invariant Vα24+ natural killer T (NKT) cells, a subpopulation of NK cell-receptor (NKR-P1A)-expressing T cells with an invariant Vα24JαQ T-cell receptor (TCR), are stimulated by the glycolipid a-galactosylceramide (KRN7000), in a CD1d-dependent, TCR-mediated fashion. Little is known about invariant Vα24+ NKT cell function or mechanisms of effector activity. Evidence suggests this cell population protects against autoimmunity and has antitumor effects against leukemia and solid tumors. Materials and Methods. We compared the phenotype and function of invariant Vα24+ NKT cells, from patients with chronic myeloid leukemia (CML) and normal donors, generated by stimulation of peripheral blood mononuclear cells with α-galactosylceramide pulsed monocyte-derived dendritic cells. The CD4-CD8- (double negative) population was studied further. Results. Activated human invariant Vα24+ NKT cells were cytotoxic against autologous and allogeneic peripheral blood dendritic cells and monocyte-derived dendritic cells but not against autologous or allogeneic T-cell PHA blasts, B-cell lymphoblastoid cell lines, monocytes, or leukemic cells from patients with CML. The findings are consistent with previous observations showing the importance of CD1d in target cell recognition. None of the Vα24+ NKT cell lines expressed the NK markers CD16, CD56, CD94, or killer inhibitory receptors, but all expressed NKR-P1A. There was no difference in phenotype, function, or ease of generation of invariant Vα24+ NKT cells between normal donors and patients with CML. Conclusion. Based on our results and the previous evidence linking reduced Vα24+ NKT cells to autoimmunity, we propose that double-negative Vα24+ NKT cells have important immune regulatory functions, including contribution to the prevention of excessive antigen stimulation by virtue of cytotoxic activity against antigen presenting cells, particularly in dendritic cells. Copyright (C) 2000 International Society for Experimental Hematology.

Original languageEnglish (US)
Pages (from-to)276-282
Number of pages7
JournalExperimental Hematology
Volume28
Issue number3
DOIs
StatePublished - Mar 1 2000
Externally publishedYes

Keywords

  • CD1d
  • Cytotoxic activity
  • NKR-P1A
  • Vα24+ natural killer T cells
  • α-Galactosylceramide

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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