Cancer Immunology, Immunotherapy

, Volume 52, Issue 10, pp 625–631

The effects of αGalCer-induced TCRVα24 Vβ11+ natural killer T cells on NK cell cytotoxicity in umbilical cord blood

Authors

  • Yoko Ueda
    • Department of Hematology and OncologyTokai University School of Medicine
    • Department of Hematology and OncologyTokai University School of Medicine
  • Balgansuren Gansuvd
    • Division of Transplant of ImmunologyUniversity of Alabama at Birmingham
  • Ying Yu
    • Division of Pulmonary and Critical Care Medicine, Department of MedicineUniversity of California at San Diego Medical Center
  • Aya Masui
    • Department of Cell Transplantation and Regenerative MedicineTokai University
  • Ayako Okamoto
    • Department of Hematology and OncologyTokai University School of Medicine
  • Ayako Higuchi
    • Department of Cell Transplantation and Regenerative MedicineTokai University
  • Kei Tazume
    • Department of Hematology and OncologyTokai University School of Medicine
  • Syunichi Kato
    • Department of Cell Transplantation and Regenerative MedicineTokai University
  • Tomomitsu Hotta
    • Department of Hematology and OncologyTokai University School of Medicine
Original Article

DOI: 10.1007/s00262-003-0398-3

Cite this article as:
Ueda, Y., Hagihara, M., Gansuvd, B. et al. Cancer Immunol Immunother (2003) 52: 625. doi:10.1007/s00262-003-0398-3

Abstract

Purpose

The first objective of this study was to investigate in vitro effects of α-galactosylceramide (αGalCer) on the proliferation of umbilical cord blood (UCB) natural killer T (NKT) cells and enhancement of their cytotoxicity. The second one is to examine whether purified NKT cells could affect the cytotoxicity of UCB-NK cells either in the presence or absence of dendritic cells (DCs).

Methods

Mononuclear cells (MNCs) from UCB were cultured for 2 weeks in the presence of IL-2 (100 U/ml), with or without αGalCer. The effect of neutralizing monoclonal antibodies (MoAb) against TCRVα24 and CD1d was also examined. TCRVα24 Vβ11 double positive NKT cells were purified by FACS sorter and then cocultured with syngeneic isolated UCBCD56+NK cells in either the presence or absence of DCs. The cytotoxicity against various malignant cell targets and cytokine production was determined.

Results

The addition of αGalCer induced human NKT cells to proliferate in UCB-MNCs to a greater extent than in adult PB-MNCs. However, it suppressed the cytotoxic activity against malignant cell targets. Anti-TCRVα24 and CD1d MoAb recovered the cytotoxicity by inhibiting the proliferation of UCB-NKT cells. NKT cells cocultured with auto-DCs significantly increased NK cell cytotoxicity against K562, and Raji cells and produced IFN-γ at much higher levels than UCB-NKT cells alone.

Conclusion

In UCB samples, αGalCer–pulsed DCs and NKT cells acted together to enhance NK cytotoxicity in vitro.

Keywords

Umbilical cord bloodαGalCerNatural killer T cellsNK cellsDendritic cells

Copyright information

© Springer-Verlag 2003