In vitro culture with IL-15 increases NK cell degranulation and enhances NK cell-mediated dendritic cell maturation
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1
UNIVERSITY OF EXTREMADURA, Spain
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2
HOSPITAL SAN PEDRO DE ALCÁNTARA, Spain
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3
IMIBIC-University of Cordoba-Hospital Reina Sofia, Spain
Natural Killer (NK) cells may play an important role in the immune response against hematological malignancies as demonstrated in the setting of stem cell transplantation. However, abnormal NK cytolytic function is observed in several hematological malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Several mechanisms are involved in this abnormal function including a decreased expression of NKp46, NKp30 and DNAM-1 activating receptors.
The aim of this study was to restore the expression of NK cell activating receptors that are downregulated in patients with hematological malignancies. Therefore, we have analyzed in vitro the effect of IL-15, IL-2 and TGF-β on NK cell phenotype and function in healthy donors and in AML and MDS patients. Our results showed that, similar to IL-2, IL-15 increased the surface expression of NKp30 whereas the expression of NKp46 and DNAM-1 was not affected. In contrast, TGF-β induced a decrease of NKp30 and did not affect the expression of NKp46 and NKG2D. IL-15 activated NK cells displayed a higher degranulation in response to the erythroleukemic cell line K562. We also observed an increased capacity of IL-15 activated NK cells to induce dendritic cell (DC) maturation probably due to the increased expression of NKp30, a receptor involved in NK-DC interactions.
In conclusion, our in vitro model supports the role of IL-15 regulating NK cell cytotoxic function and improving NK cell capacity to induce DC maturation. Further studies are required for integrating IL-15 activated NK cells into NK cell-based immunotherapeutic strategies.
Keywords:
NK cell receptors,
Cytokines,
Acute Myeloid Leukemia,
Immunotherapy,
IL-15
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
SANCHEZ CORREA
B,
BERGUA
JM,
CAMPOS
C,
ARCOS
M,
BAÑAS
H,
MORGADO
S,
SANCHEZ MATEOS
S,
GORDILLO
J,
GARCIA CASADO
J and
TARAZONA
R
(2013). In vitro culture with IL-15 increases NK cell degranulation and enhances NK cell-mediated dendritic cell maturation.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00775
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Received:
13 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. BEATRIZ SANCHEZ CORREA, UNIVERSITY OF EXTREMADURA, CACERES, Cáceres, 10003, Spain, beatrizsanchezcorrea@gmail.com