Effect of cyclosporin A on interleukin-15-activated umbilical cord blood natural killer cell function
Cytotherapy, ISSN: 1465-3249, Vol: 10, Issue: 4, Page: 397-405
2008
- 15Citations
- 17Captures
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Metrics Details
- Citations15
- Citation Indexes15
- 15
- CrossRef14
- Captures17
- Readers17
- 17
Article Description
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.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S1465324908701920; http://dx.doi.org/10.1080/14653240802129885; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=47249128109&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/18574772; https://linkinghub.elsevier.com/retrieve/pii/S1465324908701920; https://dx.doi.org/10.1080/14653240802129885
Elsevier BV
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