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

Autor: Jean Villard, Jean-Michel Dayer, Gregory Schneiter, Sylvie Ferrari-Lacraz, Casimir de Rham, Sabrina Jendly
Rok vydání: 2007
Předmět:
Cytotoxicity
Immunologic
Cell Proliferation/drug effects
Interleukin 21
0302 clinical medicine
Receptors
KIR
Killer Cells
Natural/classification/cytology/drug effects/immunology
Cytotoxicity
Immunologic/drug effects
Immunology and Allergy
Recombinant Proteins/pharmacology
Receptors
Immunologic
ddc:616
Interleukin-15
0303 health sciences
Janus kinase 3
Drug Synergism
Natural killer T cell
Recombinant Proteins
3. Good health
Cell biology
Killer Cells
Natural
medicine.anatomical_structure
Interleukin 12
Cytokines
Inflammation Mediators
Research Article
Interleukin-15/pharmacology
Immunology
Receptors
KIR/genetics/metabolism
In Vitro Techniques
Biology
Interleukins/pharmacology
Natural killer cell
Interferon-gamma
03 medical and health sciences
Interferon-gamma/biosynthesis
Rheumatology
medicine
Humans
Antigen-presenting cell
Cytokines/pharmacology
Cell Proliferation
030304 developmental biology
Lymphokine-activated killer cell
Natural Cytotoxicity Triggering Receptor 2
Interleukins
NKG2D
Inflammation Mediators/pharmacology
Receptors
Immunologic/genetics/metabolism
Interleukin-2
Interleukin-2/pharmacology
030215 immunology
Zdroj: Arthritis Research & Therapy
Arthritis Research and Therapy, Vol. 9, No 6 (2007) P. R125
ISSN: 1478-6354
DOI: 10.1186/ar2336
Popis: 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.
Databáze: OpenAIRE
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