CD137
细胞生物学
K562细胞
细胞生长
细胞
信号转导
细胞培养
生物
T细胞
化学
免疫学
白细胞介素21
免疫系统
生物化学
遗传学
作者
Laurent Vidard,Christine Dureuil,Jérémy Baudhuin,Lionel Vescovi,Laurence Durand,Véronique Sierra,Eric Parmantier
出处
期刊:Journal of Immunology
[American Association of Immunologists]
日期:2019-06-14
卷期号:203 (3): 676-685
被引量:78
标识
DOI:10.4049/jimmunol.1801137
摘要
Abstract To understand and dissect the mechanisms driving human NK cell proliferation, we exploited the methodology used in cell therapy to numerically expand NK cells in the presence of K562-derived artificial APC (aAPCs) and cytokines. For four consecutive weeks, high expression of CD137L by a K562-derived aAPC cell line could sustain NK cell expansion by 3 × 105–fold, whereas low expression of CD137L by the parental K562 cell line only supported the expansion by 2 × 103–fold. The level of expression of CD137L, however, did not modulate the sensitivity of K562 cells to the intrinsic cytotoxicity of NK cells. Similarly, the low NK cell proliferation in the presence of the parental K562 cell line and cytokines was increased by adding agonistic anti-CD137 Abs to levels similar to CD137L-expressing K562-derived aAPCs. Finally, synergy between IL-15 and IL-21 was observed only upon CD137 engagement and the presence of aAPCs. Therefore, we conclude that NK cell proliferation requires cell-to-cell contact, activation of the CD137 axis, and presence of IL-15 (or its membranous form) and IL-21. By analogy with the three-signal model required to activate T cells, we speculate that the cell-to-cell contact represents “signal 1,” CD137 represents “signal 2,” and cytokines represent “signal 3.” The precise nature of signal 1 remains to be defined.
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