Cytotoxicity of Human Cord Blood Natural Killer Cells is Enhanced by Recombinant Interleukin-15

Abstract

Hematopoietic cord blood (CB) stem cell transplantation has more advantages to other cell sources because of lower Graft Versus Host Disease (GVHD). Interleukin-15(IL-15) is an immunoregulatory cytokine, known to enhance cytolytic function of cord Natural Killer (NK) cells. The aim of this study was to investigate the effect of IL-15 on NK cytotoxicity simultaneously in different cell death stages.
We compared the ability of IL-15 to enhance the NK cytotoxicity of CB in comparison to adult blood Mononuclear Cells (MNCs) against K562 target cells by co-staining with AnnexinV-FITC and Propidium Iodide after 3.5 h incubation at 37C and 5% CO2 by using flow cytometric method. We also evaluated phenotypic changes after treatment by IL-15 in both cell sources.
Our results indicated that CB samples had lower level of apoptosis, while necrosis was negligible; also by escalating Effector: Target (E: T), we got higher level of apoptosis and necrosis in peripheral blood (PB). NK activity of cord and adult MNCs was enhanced by incubation with IL-15 (10 ng/ml) for 72 h with significantly higher results of PB in comparison to CB (p<0.0001). Moreover, IL-15 increased the percentage of CD3-/CD56+ and CD25+ cells after 72 h incubation. Results showed incubation with human recombinant (hr) IL-15 for 3 days increased NK activity.
Taken together, these results indicated that NK cytotoxicity of CB MNCs could be augmented by human recombinant (hr) IL-15, but this activity did not reach to same level of PB counterparts.
We established that CD25 expression on CB MNCs could be increased with IL-15, in 72-hour cultures, but to a lesser degree compared to that on corresponding adult PB MNCs.