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Effect of cyclosporin A on interleukin-15-activated umbilical cord blood natural killer cell function
- Source :
- Cytotherapy. 10(4)
- Publication Year :
- 2008
-
Abstract
- Interleukin (IL)-15-activated natural killer (NK) cells may provide a graft-versus-leukemia (GvL) effect post-umbilical cord blood (CB) transplantation. The effect of cyclosporin A (CsA), a calcineurin-inhibitor used for prophylaxis of graft-versus-host disease (GvHD), on IL-15-mediated activation, cytotoxic function and target-induced apoptosis of CB NK cells, was examined in comparison with adult peripheral blood (APB) NK cells.CsA was added to anti-CD3+/-IL-15-stimulated CB and APB mononuclear cells (MNC) for a 5-day incubation. CD3- CD56+ NK cell recovery was determined by flow cytometric analysis. Magnetic bead-purified CB and APB NK cells were stimulated with IL-15 for 18 h under the influence of CsA. NK activation (CD69), K562 cytotoxicity and NK-K562 interactions (CD54, perforin and annexin-V expression 4 h following contact with K562 cells) were assessed by flow cytometry.CsA decreased CD3- CD56+ NK cell recovery in anti-CD3-stimulated CB MNC 5-day cultures, an effect that could be counteracted by IL-15; comparable effects were observed with APB. Short-term (18-h) experiments revealed that CsA down-regulated K562 cytotoxicity of IL-15-activated (P=0.018) but not resting (P=0.268) purified CB NK cells. IL-15-induced CB NK CD69 expression showed increased CsA sensitivity over APB (P=0.012). CsA down-regulated K562 cell-induced CD54 (P=0.028) but not perforin (P=0.416) expression of IL-15-activated CB NK cells. Target-induced apoptosis of IL-15-activated CB (P=0.043) but not APB (P=0.144) NK cells was decreased by CsA.We have demonstrated differential CsA sensitivity of IL-15-activated CB and APB NK cells. These results may be used to improve the design of IL-15-activated NK cell adoptive immunotherapy in cancer patients receiving CsA post-CB transplantation.
- Subjects :
- Cytotoxicity, Immunologic
Cancer Research
CD3 Complex
Immunology
Graft vs Host Disease
chemical and pharmacologic phenomena
Pharmacology
Immunotherapy, Adoptive
Interleukin 21
Mice
Cyclosporin a
Immunology and Allergy
Animals
Humans
Genetics (clinical)
Cells, Cultured
Interleukin-15
Transplantation
Lymphokine-activated killer cell
biology
Chemistry
Cell Biology
Natural killer T cell
Fetal Blood
CD56 Antigen
Killer Cells, Natural
Oncology
Perforin
Interleukin 15
Cord blood
biology.protein
Interleukin 12
Cyclosporine
K562 Cells
Immunosuppressive Agents
Subjects
Details
- ISSN :
- 14772566
- Volume :
- 10
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cytotherapy
- Accession number :
- edsair.doi.dedup.....de66b43df6fdf4515e43c01f43950ed2