Short-term cytolytic mediators' expression in decidual lymphocytes is enhanced by interleukin-15

Am J Reprod Immunol. 2006 Mar;55(3):217-25. doi: 10.1111/j.1600-0897.2005.00351.x.

Abstract

Problem: We investigated whether decidual adherent cells (DAC) and interleukin (IL)-15, in comparison to interleukin (IL)-2 affect cytolytic potential of first trimester decidual lymphocytes (DL).

Method of study: Decidual mononuclear cells were obtained by enzymatic digestion and density gradient centrifugation. Non-adherent DL were collected after 2-hr adherence and cultured for 18 or 72 hr with: IL-15 (0.5-5 ng/mL), IL-2 (100-1000 U/mL) or both of these cytokines, DAC (ratio 3:1 and 1:1) or DAC and anti-IL-15 antibody. Perforin, Fas ligand (FasL) and granzyme B were detected at mRNA level in indicated culture conditions. Cytolytic activity of DL against K-562, P815 and P815-Fas was measured by 2-hr PKH-26 cytotoxicity assay. The dynamics of perforin protein and mRNA expression were measured in DL after a contact with K-562 targets.

Results: Interleukin-15 enhanced perforin, FasL and granzyme B transcription after 18-hr culture and prevented perforin protein downregulation, observed after DL culture. IL-2 had similar effects. DAC sustained perforin expression in DL and anti-IL-15 monoclonal antibody abrogated this effect. DAC increased cytotoxicity of DL against K-562 which was mediated by IL-15.

Conclusion: Interleukin-15, probably produced by DAC, upregulates cytolytic mediators' expression and perforin-mediated cytotoxicity of DL, with equal efficiency as high concentrations of IL-2.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Decidua / cytology
  • Decidua / drug effects
  • Decidua / immunology*
  • Fas Ligand Protein
  • Female
  • Gene Expression Regulation / drug effects
  • Granzymes
  • Humans
  • Interleukin-15 / immunology
  • Interleukin-15 / pharmacology*
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology*
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • RNA, Messenger / drug effects
  • RNA, Messenger / immunology
  • Reference Values
  • Serine Endopeptidases / drug effects
  • Serine Endopeptidases / genetics*
  • Serine Endopeptidases / immunology
  • Time Factors
  • Tumor Necrosis Factors / genetics*
  • Tumor Necrosis Factors / immunology
  • Up-Regulation

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • Interleukin-15
  • Interleukin-2
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • RNA, Messenger
  • Tumor Necrosis Factors
  • Perforin
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases