Scientific article
Open access

The proinflammatory cytokines IL-2, IL-15 and IL-21 modulate the repertoire of mature human natural killer cell receptors

Published inArthritis Research and Therapy, vol. 9, no. 6, R125
Publication date2007

Natural killer (NK) cells play a crucial role in the immune response to micro-organisms and tumours. Recent evidence suggests that NK cells also regulate the adaptive T-cell response and that it might be possible to exploit this ability to eliminate autoreactive T cells in autoimmune disease and alloreactive T cells in transplantation. Mature NK cells consist of a highly diverse population of cells that expresses different receptors to facilitate recognition of diseased cells and possibly pathogens themselves. Ex vivo culture of NK cells with cytokines such as IL-2 and IL-15 is an approach that permits significant expansion of the NK cell subpopulations, which are likely to have potent antitumour, antiviral, or immunomodulatory effects in autoimmunity. Our data indicate that the addition of IL-21 has a synergistic effect by increasing the numbers of NK cells on a large scale. IL-2 and IL-15 may induce the expression of killer cell immunoglobulin-like receptors (KIRs) in KIR-negative populations, the c-lectin receptor NKG2D and the natural cytotoxic receptor NKp44. The addition of IL-21 to IL-15 or IL-2 can modify the pattern of the KIR receptors and inhibit NKp44 expression by reducing the expression of the adaptor DAP-12. IL-21 also preserved the production of interferon-gamma and enhanced the cytotoxic properties of NK cells. Our findings indicate that the proinflammatory cytokines IL-2, IL-15 and IL-21 can modify the peripheral repertoire of NK cells. These properties may be used to endow subpopulations of NK cells with specific phenotypes, which may be used in ex vivo cellular immunotherapy strategies.

  • Cell Proliferation/drug effects
  • Cytokines/pharmacology
  • Cytotoxicity, Immunologic/drug effects
  • Drug Synergism
  • Humans
  • In Vitro Techniques
  • Inflammation Mediators/pharmacology
  • Interferon-gamma/biosynthesis
  • Interleukin-15/pharmacology
  • Interleukin-2/pharmacology
  • Interleukins/pharmacology
  • Killer Cells, Natural/classification/cytology/drug effects/immunology
  • Natural Cytotoxicity Triggering Receptor 2
  • Receptors, Immunologic/genetics/metabolism
  • Receptors, KIR/genetics/metabolism
  • Recombinant Proteins/pharmacology
  • Swiss National Science Foundation - 310000-108453
  • Swiss National Science Foundation - PMPDA-110347
Citation (ISO format)
DE RHAM, Casimir et al. The proinflammatory cytokines IL-2, IL-15 and IL-21 modulate the repertoire of mature human natural killer cell receptors. In: Arthritis Research and Therapy, 2007, vol. 9, n° 6, p. R125. doi: 10.1186/ar2336
Main files (1)
Article (Published version)
ISSN of the journal1478-6354

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