Selective expansion and engraftment of human CD16+ NK cells in NOD/SCID mice
Selective expansion and engraftment of human CD16+ NK cells in NOD/SCID mice
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DOI：
10.1002/eji.200535125
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发表时间：
2005-12-01
影响因子：
5.4
通讯作者：
Okada, S
中科院分区：
文献类型：
--
作者：
Harada, H;Suzu, S;Okada, S
NK 细胞是大颗粒淋巴细胞，代表先天免疫的关键组成部分。由于缺乏合适的动物模型，人类 NK 细胞功能的研究主要基于体外测定。在这里，我们建立了在接受脐带血单核细胞 (CBMC) 移植物和 GFP 转导的 HFWT 诱导 NK 细胞 (GHINK-1) 的 NOD/SCID（严重联合免疫缺陷）小鼠中发育人类 NK 细胞的条件，这些条件已被证明支持体外从人 PBMC 和 CBMC 中选择性扩增 NK 细胞。小鼠外周血(PB)、腹膜腔脾脏、骨髓和肝脏中出现大量CD56(dim)CD16(+)细胞毒性细胞和CD56(-)CD16(+)未成熟NK细胞。新生成的 NK 细胞不表达 CD25、CD69 和 NKp44 等激活标记物，这些标记物的表达在体外被 IL-2 增强。移植人 NK 细胞的 NOD/SCID 小鼠在体外和体内均表现出针对 K562 红白血病的抗肿瘤活性。因此，我们成功地在 NOD/SCID 小鼠中开发了 CD56(dim)-CD16(+) 细胞毒性 NK 细胞群，与人 PB 和 CD56(-)CD16(+) 未成熟 NK 细胞中的主要 NK 部分非常相似。我们的模型不仅提供有关生理性人类 NK 细胞的发育和动态的信息，而且还提供免疫治疗策略的重要临床前系统。
NK cells are large granular lymphocytes that represent a critical component of the innate immunity. Investigations of human NK cell function are largely based on in vitro assays because of the lack of suitable animal models. Here we have established conditions leading to the development of human NK cells in NOD/SCID (severe combined immunodeficiency) mice receiving grafts of cord blood mononuclear cells (CBMC), and GFP-transduced HFWT inducing NK cells (GHINK-1), which have been shown to support the selective expansion of NK cells from human PBMC and CBMC in vitro. Significant numbers of CD56(dim)CD16(+) cytotoxic and CD56(-)CD16(+) immature NK cells appeared in peripheral blood (PB), peritoneal cavity spleen, bone marrow and liver of the mice. The newly generated NK cells did not express activation markers such as CD25, CD69 and NKp44, the expression of which was augmented by IL-2 in vitro. The NOD/SCID mice engrafted with human NK cells exhibited antitumor activity against K562 erythroleukemia in vitro and in vivo. Thus, we succeeded in developing a CD56(dim)-CD16(+) cytotoxic NK cell populations in NOD/SCID mice closely resembling the main NK fraction in human PB and CD56(-)CD16(+) immature NK cells. Our model provides not only information about the development and dynamics of physiological human NK cells but also an important pre-clinical system for immunotherapeutic strategies.