Scientific publications

Interleukin-15 liver gene transfer increases the number and function of IKDCs and NK cells

Arina A, Murillo O, Dubrot J, Azpilikueta A, Gabari I, Perez-Gracia JL [SP], Alfaro C, Berasain C, Prieto J, Ferrini S, Hervas-Stubbs S, Melero I [SP].
Gene Therapy Unit, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain

Magazine: Gene Therapy

Date: Apr 1, 2008

Medical Oncology Immunology [SP] Hepatology

The surface phenotype CD3-NK1.1+DX5+CD11c(int)B220+GR1- has been recently ascribed to a novel subset of mouse leukocytes termed interferon (IFN)-producing killer dendritic cells (IKDCs) that shares functions with natural killer (NK) cells and DCs. Interleukin-15 (IL-15) is critical for NK cells but its relationship with IKDC remained unexplored.

An expression cassette encoding human IL-15 (hIL-15) has been transferred by hydrodynamic injection into the liver of mice, resulting in transient expression of the cytokine that is detectable during the first 48 h. hIL-15 hydrodynamic gene transfer resulted in an expansion of NK cells and IKDCs.

Relative expansions of IKDCs were more dramatic in the IL-15 gene-transferred hepatic tissue than in the spleen. Adoptively transferred DX5+ cells comprising both NK cells and IKDCs proliferated in response to hydrodynamic injection of hIL-15, indicating that quantitative increases are at least in part the result of proliferation from already differentiated cells. Expansion is accompanied by enhanced cytolytic activity and increased expression of TRAIL and CD137 (4-1BB), without augmenting interferon-gamma production.

The effects of a single hydrodynamic injection surpassed those of two intraperitoneal doses of the recombinant protein. The novel functional link between circulating IL-15 and IKDCs opens new possibilities to study the biology and applications of this minority cell subset.

CITATION Gene Ther. 2008 Apr;15(7):473-83

you maybe interested


The Clínica is the greater private hospital with technological equipment of Spain, all in a single center.

Imagen de un PET, tecnología de vanguardia en la Clínica Universidad de Navarra


The professionals of the Clínica perform continuous research and training, always to the benefit of the patient.

Imagen profesionales de la Clínica Universidad de Navarra


Learn why we are different from other healthcare centers. Quality, speed, comfort and results.

Imagen del edificio de la Clínica Universidad de Navarra