Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells
Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells
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DOI：
10.1182/blood-2006-04-020198
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发表时间：
2006-12-01
期刊：
影响因子：
20.3
通讯作者：
Verneris, Michael R.
中科院分区：
文献类型：
--
作者：
Grzywacz, Bartosz;Kataria, Nandini;Verneris, Michael R.
人类自然杀伤（NK）细胞分化的阶段尚未完全确定。用白细胞介素7（IL-7）、IL-15、干细胞因子（SCF）、FLT-3L和小鼠胎肝细胞系（EL08.1D2）培养CD 34（+）祖细胞，我们鉴定了基于CD 117和CD 94的分化CD 56（+）细胞的两个非重叠亚群（CD 117（high）CD 94（-）和CD 117（low/-）CD 94（+）细胞）。两个群体均表达CD 161和NKp 44，但在NKp 30、NKp 46、NKG 2A、NKG 2C、NKG 2D、CD 8、CD 16和KIR方面存在差异。仅CD 117（低/-）CD 94（+）群体显示细胞毒性和干扰素-γ产生。两个细胞群均来源于单个CD 34（+）CD 38（-）Lin（-）细胞，其百分比随时间以相反的方式变化，其中CD 117（高）CD 94（-）细胞在早期占优势，并由于CD 117（低/-）CD 94（+）细胞群的增加而减少。这2个亚群代表NK细胞分化的不同阶段，因为纯化的CD 117（高）CD 94（-）细胞产生CD 117（低/-）CD 94（+）细胞。基质细胞系（EL08.1D2）通过中间表型（CD 117（高）CD 94（低/-））促进从CD 117（高）CD 94（-）向CD 117（低/-）CD 94（+）的转变。EL08.1D2还保持了成熟表型，防止了CD 117（低/-）CD 94（+）细胞逆转为中间（CD 117（低）CD 94（低/-））表型。在脐带血中发现了类似的CD 56 * CD 117（高）CD 94（-）细胞群。INK细胞分化的确定阶段为HLA特异性抑制性受体（即，CD 94/NKG 2A）的协调获得和在发育人类INK细胞中的功能提供了证据。
The stages of human natural killer (NK) cell differentiation are not well established. Culturing CD34(+) progenitors with interleukin 7 (IL-7), IL-15, stem cell factor (SCF), FLT-3L, and murine fetal liver cell line (EL08.1D2), we identified 2 nonover-lapping subsets of differentiating CD56(+) cells based on CD117 and CD94 (CD117(high)CD94(-) and CD117(low/-)CD94(+) cells). Both populations expressed CD161 and NKp44, but differed with respect to NKp30, NKp46, NKG2A, NKG2C, NKG2D, CD8, CD16, and KIR. Only the CD117(low/-)CD94(+) population displayed cytotoxicity and interferon-gamma production. Both populations arose from a single CD34(+)CD38(-)Lin(-) cell and their percentages changed over time in a reciprocal fashion, with CD117(high)CD94(-)cells predominating early and decreasing due to an increase of the CD117(low/-)CD94(+) population. These 2 subsets represent distinct stages of NK-cell differentiation, since purified CD117(high)CD94(-) cells give rise to CD117(low/-)CD94(+) cells. The stromal cell line (EL08.1D2) facilitated the transition from CD117(high)CD94(-) to CD117(low/-)CD94(+) via an intermediate phenotype (CD117(high)CD94(low/-)). EL08.1D2 also maintained the mature phenotype, preventing the reversion of CD117(low/-)CD94(+) cells to the intermediate (CD117(low)CD94(low/-)) phenotype. An analogous population of CD56*CD117(high)CD94(-) cells was found in cord blood. The identif led stages of IN K-cell differentiation provide evidence for coordinated acquisition of HLA-specific inhibitory receptors (ie, CD94/NKG2A) and function in developing human INK cells.