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

  • Yoko Ueda
  • Masao Hagihara
  • Balgansuren Gansuvd
  • Ying Yu
  • Aya Masui
  • Ayako Okamoto
  • Ayako Higuchi
  • Kei Tazume
  • Syunichi Kato
  • Tomomitsu Hotta
Original Article

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 blood αGalCer Natural killer T cells NK cells Dendritic cells 

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Yoko Ueda
    • 1
  • Masao Hagihara
    • 1
  • Balgansuren Gansuvd
    • 3
  • Ying Yu
    • 4
  • Aya Masui
    • 2
  • Ayako Okamoto
    • 1
  • Ayako Higuchi
    • 2
  • Kei Tazume
    • 1
  • Syunichi Kato
    • 2
  • Tomomitsu Hotta
    • 1
  1. 1.Department of Hematology and OncologyTokai University School of MedicineIseharaJapan
  2. 2.Department of Cell Transplantation and Regenerative MedicineTokai UniversityIseharaJapan
  3. 3.Division of Transplant of ImmunologyUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Division of Pulmonary and Critical Care Medicine, Department of MedicineUniversity of California at San Diego Medical CenterSan DiegoUSA

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