[Cytotoxicity of IFN-gamma-activated dendritic cells to freshly isolated acute myeloid leukemia cells]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005 Dec;13(6):1071-5.
[Article in Chinese]

Abstract

To investigate the tumoricidal activity of dendritic cell (DC) stimulated by interferon-gamma (IFN-gamma) against freshly isolated myeloid leukemia cells and its mechanism, the peripheral blood monocytes collected from healthy donors were cocultured with interleukin-4 and granulocyte-macrophage colony-stimulating factor in medium to induce DC for 7 days. After 12 hour culture in the absence or presence of IFN-gamma, the changes of costimulatory molecules were analyzed with flow cytometry. To assay the cytotoxicity of DC against freshly isolated acute myeloid cells, they were cocultured at various effector-to-target ratio for 18 hours, then the percentage of tumoricidal activity was measured with (51)Cr release assay. To explore the mechanism of DC-mediated cytotoxicity, the change of DC surface or intracellular protein expression of Fas ligand (Fas L), TNF-alpha and TNF related apoptosis-inducing ligand (TRAIL) were analyzed with flow cytometry. The results showed that IFN-gamma enhanced cytotoxicity of DC against AML cells was (33.8 +/- 1.6)% at E:T as 20:1, compared with unstimulated DC (P < 0.05); IFN-gamma up-regulated expression of costimulatory molecules of DC surface such as CD86 and CD83; after stimulation with IFN-gamma, expression of intracellular TRAIL of DC was significantly enhanced, but expression of TRAIL on cell surface of DC was low; while the significant changes of Fas L and TNF-alpha expression neither on cell surface or in cells were not observed before or after stimulation with IFN-gamma. It is concluded that DC stimulated by IFN-gamma exhibit tumoricidal activity against AML cells. The cytotoxicity is partially related to maturation of DC and TRAIL inducing apoptosis, but not associated with death domain-independent mechanism of Fas L and TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Antigens, CD / analysis
  • B7-2 Antigen / analysis
  • CD83 Antigen
  • Coculture Techniques
  • Cytotoxicity, Immunologic / drug effects*
  • Cytotoxicity, Immunologic / immunology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Fas Ligand Protein / analysis
  • Flow Cytometry
  • Humans
  • Immunoglobulins / analysis
  • Interferon-gamma / pharmacology*
  • Leukemia, Myeloid / immunology
  • Leukemia, Myeloid / pathology
  • Membrane Glycoproteins / analysis
  • TNF-Related Apoptosis-Inducing Ligand / analysis
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Antigens, CD
  • B7-2 Antigen
  • Fas Ligand Protein
  • Immunoglobulins
  • Membrane Glycoproteins
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma