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

Authors: Dong-Pyo DP. Lim, Youn-Young YY. Jang, Seokho S. Kim, Sang Seok SS. Koh, Je-Jung JJ. Lee, Ju-Sun JS. Kim, Minh-Trang MT. Thi Phan, Dong-Jun DJ. Shin, Myung-Geun MG. Shin, Seung-Hwan SH. Lee, Meesun M. Yoon, Sang-Ki SK. Kim, Jung-Han JH. Yoon, Min-Ho MH. Park, Duck D. Cho
Published: 06/18/2014, Cytotherapy

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.


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.


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).


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.

Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
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