Altered functions of natural killer cells in response to L-Arginine availability

Cell Immunol. 2012 Dec;280(2):182-90. doi: 10.1016/j.cellimm.2012.11.018. Epub 2012 Dec 19.


L-Arginine (L-Arg) availability is crucial in the regulation of immune response. Indeed, L-Arg deficiency induces T-cell dysfunction and could modulate the properties of natural killer (NK) cells involved in the early host defense against infections and tumors. We explored the impact of L-Arg depletion on NK cell functions using two models - an NK-92 cell line and isolated human blood NK cells. Below 5mg/L of L-Arg, NK-92 cell proliferation was decreased and a total L-Arg depletion reduced NK-92 cell viability. NK cell cytotoxicity was significantly inhibited in presence of low L-Arg concentration (2.5 mg/L). L-Arg depletion reduced the expression of NK-92 activating receptors, NKp46 and NKp30, the expression of NK ζ chain and the NK-92 intracellular production of IFN-γ. Whatever the L-Arg concentrations tested, no significant variation in the gene expression of transporters and enzymes involved in L-Arg metabolism was found. Thus, L-Arg availability modulates the phenotypic and functional properties of NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / physiology*
  • Cytotoxicity, Immunologic
  • Humans
  • Interferon-gamma / biosynthesis
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Natural Cytotoxicity Triggering Receptor 1 / analysis
  • Natural Cytotoxicity Triggering Receptor 3 / analysis


  • NCR1 protein, human
  • NCR3 protein, human
  • Natural Cytotoxicity Triggering Receptor 1
  • Natural Cytotoxicity Triggering Receptor 3
  • Interferon-gamma
  • Arginine