Influence of in vitro IL-2 or IL-15 alone or in combination with Hsp-70-derived 14-mer peptide (TKD) on the expression of NK cell activatory and inhibitory receptors

Mediators Inflamm. 2013:2013:405295. doi: 10.1155/2013/405295. Epub 2013 Feb 17.

Abstract

NK cells represent a potential tool for adoptive immunotherapy against tumors. Membrane-bound Hsp70 acts as a tumor-specific marker enhancing NK cell activity. Using flow cytometry the effect of in vitro stimulation with IL-2 or IL-15 alone or in combination with Hsp70-derived 14-mer peptide (TKD) on cell surface expression of NK activatory receptors (CD16, NKG2D, NKG2C, NKp46, NKp44, NKp30, KIR2DL4, DNAM-1, and LAMP1) and NK inhibitory receptors (NKG2A, KIR2DL2/L3, LIR1/ILT-2, and NKR-P1A) in healthy individuals was studied. Results were expressed as the percentage of receptor expressing cells and the amount of receptor expressed by CD3(-)CD56(+) cellular population. CD94, NKG2D, NKp44, NKp30, KIR2DL4, DNAM-1, LAMP1, NKG2A, and NKR-P1A were upregulated after the stimulation with IL-2 or IL-15 alone or in combination with TKD. KIR2DL2/L3 was upregulated only by IL-15 and IL-15/TKD. Concurrently, an increase in a number of NK cells positive for CD94, NKp44, NKp30, KIR2DL4, and LAMP1 was observed. IL-15 and IL-15/TKD caused also cell number rise positive for KIR2DL2/L3 and NKR-P1A. Cell number positive for NKG2C and NKG2A was increased only by IL-2 and IL-2/TKD. The diverse effect of IL-2 or IL-15 w or w/o TKD on cell surface expression was observed in CD16, NKp46, and LIR1/ILT-2.

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Cells, Cultured
  • HSP70 Heat-Shock Proteins / chemistry*
  • Humans
  • Interleukin-15 / pharmacology*
  • Interleukin-2 / pharmacology*
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / metabolism*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Lysosomal Membrane Proteins / metabolism
  • NK Cell Lectin-Like Receptor Subfamily B / metabolism
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism
  • Natural Cytotoxicity Triggering Receptor 2 / metabolism
  • Natural Cytotoxicity Triggering Receptor 3 / metabolism
  • Peptides / chemistry*
  • Peptides / pharmacology*
  • Receptors, IgG / metabolism
  • Receptors, KIR2DL2
  • Receptors, KIR2DL4 / metabolism

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen
  • HSP70 Heat-Shock Proteins
  • Interleukin-15
  • Interleukin-2
  • KIR2DL2 protein, human
  • KIR2DL4 protein, human
  • KLRB1 protein, human
  • KLRC2 protein, human
  • KLRK1 protein, human
  • LAMP1 protein, human
  • Lysosomal Membrane Proteins
  • NCR1 protein, human
  • NCR2 protein, human
  • NCR3 protein, human
  • NK Cell Lectin-Like Receptor Subfamily B
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily K
  • Natural Cytotoxicity Triggering Receptor 1
  • Natural Cytotoxicity Triggering Receptor 2
  • Natural Cytotoxicity Triggering Receptor 3
  • Peptides
  • Receptors, IgG
  • Receptors, KIR2DL2
  • Receptors, KIR2DL4