IL-15 improves the cytotoxicity of cytokine-induced killer cells against leukemia cells by upregulating CD3+CD56+ cells and downregulating regulatory T cells as well as IL-35

J Immunother. 2013 Nov-Dec;36(9):462-7. doi: 10.1097/CJI.0000000000000001.

Abstract

Cytokine-induced killer (CIK) cells are usually generated from peripheral blood mononuclear cells with the stimulation of IL-2 in vitro. Unlike the conventional IL-2-stimulated CIK cells (IL-2-CIK cells), we investigated the characteristics and potential mechanism of IL-15-stimulated CIK cells (IL-15-CIK cells) in this study. Compared with IL-2-CIK cells, the percentage of CD3CD56 cells was significantly increased in IL-15-CIK cells, but the expression of regulatory T (Treg) cells and IL-35 was significantly decreased in IL-15-CIK cells. Meanwhile, the in vitro cytotoxicity against human myeloid leukemia cells K562 of IL-15-CIK cells was significantly augmented compared with IL-2-CIK cells. These data suggest that IL-15 may improve the cytotoxicity of CIK cells against leukemia cells by upregulating CD3CD56 cells and downregulating Treg cells and IL-35.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CD56 Antigen / immunology
  • CD56 Antigen / metabolism
  • Cells, Cultured
  • Cytokine-Induced Killer Cells / immunology*
  • Cytotoxicity, Immunologic / drug effects
  • Cytotoxicity, Immunologic / immunology*
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Humans
  • Interleukin-15 / immunology*
  • Interleukin-15 / pharmacology
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacology
  • Interleukins / genetics
  • Interleukins / immunology*
  • Interleukins / metabolism
  • K562 Cells
  • Leukemia / immunology
  • Leukemia / pathology
  • Natural Killer T-Cells / drug effects
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / immunology

Substances

  • CD3 Complex
  • CD56 Antigen
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-15
  • Interleukin-2
  • Interleukins
  • interleukin-35, human