CD56(bright) natural killer cell subsets: Characterization of distinct functional responses to interleukin-2 and the c-kit ligand
CD56(bright) natural killer cell subsets: Characterization of distinct functional responses to interleukin-2 and the c-kit ligand
复制标题
DOI：
10.1002/eji.1830270203
复制
发表时间：
1997-02-01
影响因子：
5.4
通讯作者：
Caligiuri, MA
中科院分区：
文献类型：
--
作者：
Carson, WE;Fehniger, TA;Caligiuri, MA
自然杀伤(NK)细胞是骨髓来源的大颗粒淋巴细胞，表达CD56表面抗原。CD56(明亮的)NK亚群约占所有NK细胞的10%，被认为是血液中分化最低的NK细胞成分。最成熟的NK细胞低密度表达CD56，高密度表达CD16，而CD56(亮)NK细胞不表达CD16(亮)或低密度表达(CD56(亮)CD16(暗))。C-KIT是一种酪氨酸激酶受体，在CD34(+)造血祖细胞和CD56(明亮)NK细胞上均有表达。在目前的研究中，我们研究了白细胞介素2受体(IL-2R)和c-kit在CD56(BREAT)亚群中的表达。从新鲜血液中分离的CD56(亮)CD16(-)和CD56(亮)CD16(暗)NK亚群都表达高亲和力的IL-2R和c-kit受体。然而，每个CD56(明亮的)NK细胞亚群对IL-2、c-kit配体(KL)或两者都有不同的功能反应。CD56(明亮)CD16(-)NK细胞上高亲和力IL-2R的激活诱导的增殖反应明显弱于CD56(明亮)CD16(Dim)NK细胞亚群。CD56(Bright)CD16(-)NK细胞亚群与KL共同孵育可显著增强IL-2诱导的增殖反应，而KL对CD56(Bright)CD16(Dim)NK细胞亚群无明显影响。CD56(BREAT)亚群中高亲和力IL-2R的激活可诱导淋巴因子激活的杀伤细胞(LAK)活性，但KL对LAK活性无影响。CD56(明亮的)亚群与IL-12以及只饱和高亲和力IL-2R的IL-2浓度的共同刺激可诱导大量干扰素(IFN)-γ的产生。在这个共刺激信号中加入KL可以增加CD56(明亮的)NK亚群中的干扰素-γ的产生。CD56(明亮)CD16(-)和CD56(明亮)CD16(Dim)NK亚群对IL-2和KL的不同功能反应有助于深入了解IL-2R信号，并提示每个表型识别NK细胞分化的不同阶段。
Natural killer (NK) cells are bone marrow-derived large granular lymphocytes that express the CD56 surface antigen. The CD56(bright) NK subset represents approximately 10% of all NK cells and is thought to be the least differentiated NK cell component in blood. The most mature NK cell expresses CD56 at low density and CD16 (FcR gamma III) at high density, whereas CD56(bright) NK cells either lack CD16 (CD56(bright) CD16(-)) or express it at low density (CD56(bright) CD16(dim)). c-kit is a tyrosine kinase receptor which is expressed on both CD34(+) hematopoietic precursor cells and CD56(bright) NK cells. In the current study, we characterize interleukin (IL)-2 receptor (IL-2R) and c-kit expression in each of the CD56(bright) subsets. Both the CD56(bright) CD16(-) and CD56(bright) CD16(dim) NK subsets express the high-affinity IL-2R and the c-kit receptor when isolated from fresh blood. However, each CD56(bright) NK cell subset has distinct functional responses to IL-2, the c-kit ligand (KL), or both. Activation of the high-affinity IL-2R on CD56(bright) CD16(-) NK cells induces a proliferative response that is significantly weaker than that observed in the CD56(bright) CD16(dim) NK cell subset. Incubation of the CD56(bright) CD16(-) NK cell subset with KL significantly enhances IL-2-induced proliferation, while KL has no such effect on the CD56(bright) CD16(dim) NK subset. Activation of the high-affinity IL-2R in both CD56(bright) subsets induces lymphokine-activated killer (LAK) activity, but the addition of KL has no effect on LAK activity. Co-stimulation of either CD56(bright) subset with IL-12 and concentrations of IL-2 that only saturate the high-affinity IL-2R induces substantial interferon (IFN)-gamma production. The addition of KL to this co-stimulatory signal enhances IFN-gamma production in both CD56(bright) NK subsets. The distinct functional responses to IL-2 and KL seen in the CD56(bright) CD16(-) and CD56(bright) CD16(dim) NK subsets provide insight into IL-2R signaling and suggest that each phenotype identifies a discrete stage of NK cell differentiation.