Activation of NK Cells in Mixed Cultures of Wharton's Jelly Mesenchymal Stromal Cells and Peripheral Blood Lymphocytes

Bull Exp Biol Med. 2018 Jan;164(3):339-343. doi: 10.1007/s10517-018-3985-1. Epub 2018 Jan 8.

Abstract

Mesenchymal stromal cells possess immunosuppressive properties that might be used for the therapy of inflammatory diseases of various geneses. The effects of mesenchymal stromal cells depend on their lifetime in the recipient tissues. During heterologous transplantation, mesenchymal stromal cells are eliminated by NK cells. We studied NK cell formation in mixed cultures of Wharton's jelly mesenchymal stromal cells and peripheral blood lymphocytes from an autologous donor. Lymphocytes were activated by a mitogen or IL-2. The lifetime of mesenchymal stromal cells was estimated by MTT test. Cytotoxic activity and phenotype of NK cells were evaluated by flow cytometry. It was found that activation of NK cells depended on IL-2 and was registered on day 2 of incubation with IL-2. In cultures with mitogen-activated lymphocytes, cytotoxicity was observed after 5-6 days. Cytotoxicity of NK correlated with significant decrease in CD16+ and increase in CD56+ NK and with reduction of mesenchymal stromal cell viability. Thus, the main mechanism of elimination of mesenchymal stromal cells is cytotoxicity of NK cells that depended on IL-2 production.

Keywords: lymphocyte activation; mesenchymal stromal cells; natural killers.

MeSH terms

  • CD56 Antigen / genetics
  • CD56 Antigen / immunology
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Coculture Techniques
  • Cytotoxicity, Immunologic / drug effects
  • Female
  • Fetal Blood / cytology
  • Fetal Blood / immunology
  • Fetus
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / immunology
  • Gene Expression
  • Humans
  • Interleukin-2 / pharmacology*
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / drug effects*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / immunology
  • Phytohemagglutinins / pharmacology*
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology
  • Wharton Jelly / cytology
  • Wharton Jelly / immunology

Substances

  • CD56 Antigen
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Interleukin-2
  • NCAM1 protein, human
  • Phytohemagglutinins
  • Receptors, IgG