Effect of exposure to interleukin-21 at various time points on human natural killer cell culture

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Effect of exposure to interleukin-21 at various time points on human natural killer cell culture
D P Lim; Y Y Jang; Seok Ho Kim; Sang Seok Koh; J J Lee; J S Kim; M T Thi Phan; D J Shin; M G Shin; S H Lee; M Yoon; S K Kim; J H Yoon; M H Park; D Cho
Bibliographic Citation
Cytotherapy, vol. 16, no. 10, pp. 1419-1430
Publication Year
Background aims: Interleukin-21 (IL-21) can enhance the effector function of natural killer (NK) cells but also limits their proliferation when continuously combined with IL-2/IL-15. Paradoxically, membrane-bound (mb)-IL-21 has been shown to improve human NK cell proliferation when cultured with IL-2/mb-IL-15. To clarify the role of IL-21, we investigated the effect of the timing of IL-21 addition to NK cell culture. Methods: IL-2/IL-15-activated NK cells were additionally treated with IL-21 according to the following schedules; (i) control (without IL-21); (ii) first week (day 0 to day 7); (iii) intermittent (the first 3 days of each week for 7 weeks); (iv) after 1 week (day 8 to day 14); and (v) continuous (day 0 to day 49). The expression of NK receptors, granzyme B, perforin, CD107a, interferon-γ, telomere length and NK cell death were measured by flow cytometry. Results: Compared with the control (2004.2-fold; n= 10 healthy donors) and intermittent groups (2063.9-fold), a strong proliferative response of the NK cells on day 42 was identified in the "first week" group (3743.8-fold) (P< 0.05). NK cells treated with IL-21 in the "first week" group showed cytotoxicity similar to that in control cells. On day 28, there was a significant increase in cytotoxicity of "first week" NK cells that received IL-21 treatment for an additional 2 days compared with the "first week" NK cells (P< 0.05). Conclusions: These data suggest that controlling temporal exposure of IL-21 during NK cell proliferation can be a critical consideration to improve the yields and cytotoxicity of NK cells.
Natural killer cellsIL-15IL-2IL-21
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