Abstract:
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.
journal_name
Cytotherapyjournal_title
Cytotherapyauthors
Lim DP,Jang YY,Kim S,Koh SS,Lee JJ,Kim JS,Thi Phan MT,Shin DJ,Shin MG,Lee SH,Yoon M,Kim SK,Yoon JH,Park MH,Cho Ddoi
10.1016/j.jcyt.2014.04.008subject
Has Abstractpub_date
2014-10-01 00:00:00pages
1419-30issue
10eissn
1465-3249issn
1477-2566pii
S1465-3249(14)00596-9journal_volume
16pub_type
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