NKG2D functions as an activating receptor on natural killer cells in common marmoset (callithrix jacchus).

NKG2D functions as an activating receptor on natural killer cells in common marmoset (callithrix jacchus).
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NKG2D 在普通狨猴 (callithrix jacchus) 中充当自然杀伤细胞的激活受体。

DOI:
10.1093/intimm/dxu053
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发表时间:
2014
期刊:
Int Immunol.
影响因子:
--
通讯作者:
Ogasawara K.
Ogasawara K.
中科院分区:
--
文献类型:
--
作者:
Watanabe M;Kudo Y;Kawano M;Nakayama M;Nakamura K;Kameda M;Ebara M;Sato T;Nakamura M;Omine K;Kametani Y;Suzuki R;Ogasawara K.

文献摘要

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自然杀伤细胞2组膜D(NKG 2D)受体是一种NK激活受体,在宿主防御肿瘤和病毒感染中发挥重要作用。尽管绒猴是一种重要且可靠的动物模型,特别是对于人类特异性病毒感染的研究,但之前尚未对绒猴NK细胞上的NKG 2D进行功能表征。在本研究中,我们研究了表达NKG 2D并具有细胞溶解潜力的绒猴NK细胞亚群。根据其CD 16和CD 56表达模式,绒猴NK细胞可分为三个亚群:CD 16 + CD 56 −、CD 16 − CD 56+和CD 16 − CD 56 −细胞。使用由MHC I类链相关分子A(云母)-Fc融合蛋白组成的NKG 2D配体确认了绒猴CD 16 + CD 56 −和CD 16 − CD 56+脾细胞上的NKG 2D表达。当用IL-2培养绒猴脾细胞4天时,NKG 2D表达保留在CD 16 + CD 56 −和CD 16 − CD 56+上。此外,在IL-2刺激后,出现了表达NKG 2D的绒猴NK群体中的CD 16 + CD 56+细胞。IL-2激活的绒猴NK细胞对K562靶细胞和稳定表达云母的靶细胞显示出强的细胞溶解活性。此外,在添加MICA-Fc融合蛋白后,绒猴脾细胞的细胞溶解活性显著降低。因此,NKG 2D作为具有细胞毒性潜力的绒猴NK细胞上的活化受体发挥作用,绒猴NK细胞亚群的表型特征与人类中观察到的表型特征相似。
The natural killer group 2 membrane D (NKG2D) receptor is an NK-activating receptor that plays an important role in host defense against tumors and viral infections. Although the marmoset is an important and reliable animal model, especially for the study of human-specific viral infections, functional characterization of NKG2D on marmoset NK cells has not previously been conducted. In the present study, we investigated a subpopulation of marmoset NK cells that express NKG2D and exhibit cytolytic potential. On the basis of their CD16 and CD56 expression patterns, marmoset NK cells can be classified into three subpopulations: CD16+CD56−, CD16−CD56+and CD16−CD56−cells. NKG2D expression on marmoset CD16+CD56−and CD16−CD56+splenocytes was confirmed using an NKG2D ligand composed of an MHC class I chain-related molecule A (MICA)-Fc fusion protein. When marmoset splenocytes were cultured with IL-2 for 4 days, NKG2D expression was retained on CD16+CD56−and CD16−CD56+. In addition, CD16+CD56+cells within the marmoset NK population appeared which expressed NKG2D after IL-2 stimulation. IL-2-activated marmoset NK cells showed strong cytolytic activity against K562 target cells and target cells stably expressing MICA. Further, the cytolytic activity of marmoset splenocytes was significantly reduced after addition of MICA-Fc fusion protein. Thus, NKG2D functions as an activating receptor on marmoset NK cells that possesses cytotoxic potential, and phenotypic profiles of marmoset NK cell subpopulations are similar to those seen in humans.