NK cells produce high levels of IL-10 early after allogeneic stem cell transplantation and suppress development of acute GVHD.

NK cells produce high levels of IL-10 early after allogeneic stem cell transplantation and suppress development of acute GVHD.
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DOI:
10.1002/eji.201747134
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发表时间:
2018-03
影响因子:
5.4
通讯作者:
Moss P
Moss P
中科院分区:
医学3区
文献类型:
--
作者:
Chan YLT;Zuo J;Inman C;Croft W;Begum J;Croudace J;Kinsella F;Maggs L;Nagra S;Nunnick J;Abbotts B;Craddock C;Malladi R;Moss P

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自然杀伤 (NK) 细胞在同种异体干细胞移植 (allo-SCT) 后迅速重建,此时同种异体反应性 T 细胞免疫正在建立。我们研究了 82 名患者在 T 细胞耗尽的同种异体干细胞移植后的早期 NK 细胞重建情况。 NK 细胞数量迅速增加,超过了 T 细胞重建,因此 NK:T 细胞比率在第 14 天时超过 40。第 14 天的 NK 细胞 (NK-14) 是供体来源的,剧烈增殖并表达针对淋巴和外周组织的趋化因子受体。在超过 70% 的细胞中观察到免疫调节细胞因子 IL-10 的自发产生,并且细胞因子和生长因子的转录得到增强。 NK-14细胞数量与II-IV级急性移植物抗宿主病(GVHD)的发生率呈负相关。这些发现表明,allo-SCT 后第 14 天免疫调节 NK 细胞的稳健重建是临床结果的重要决定因素,表明 NK 细胞可能通过产生 IL-10 来抑制 T 细胞介导的同种异体免疫反应的发展。
Natural killer (NK) cells rapidly reconstitute following allogeneic stem cell transplantation (allo‐SCT), at the time when alloreactive T cell immunity is being established. We investigated very early NK cell reconstitution in 82 patients following T cell‐depleted allo‐SCT. NK cell number rapidly increased, exceeding T cell reconstitution such that the NK:T cell ratio was over 40 by day 14. NK cells at day 14 (NK‐14) were donor‐derived, intensely proliferating and expressed chemokine receptors targeted to lymphoid and peripheral tissue. Spontaneous production of the immunoregulatory cytokine IL‐10 was observed in over 70% of cells and transcription of cytokines and growth factors was augmented. NK‐14 cell number was inversely correlated with the incidence of grade II‐IV acute graft versus host disease (GVHD). These findings reveal that robust reconstitution of immunoregulatory NK cells by day 14 after allo‐SCT is an important determinant of the clinical outcome, suggesting that NK cells may suppress the development of the T cell‐mediated alloreactive immune response through production of IL‐10.
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