A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immature
A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immature
复制标题
DOI：
10.1182/blood-2006-07-036228
复制
发表时间：
2007-07-15
期刊：
影响因子：
20.3
通讯作者：
Miller, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Cooley, Sarah;Xiao, Feng;Miller, Jeffrey S.
受体的获得如何与自然杀伤(NK)细胞的功能成熟相关，目前还知之甚少。我们使用实时定量聚合酶链式反应(PCR)分析比较了异基因移植受者及其供者NK细胞中NKG2和KIR基因的表达。CD56(Bright)细胞增加8倍，KIR表达减弱(2DL4除外)，NKG2a增加的受者NK亚群有显著差异。在正常血液中，并不是所有的CD56(DIM)细胞都表达KIR，并定义了一个新的致力于NK细胞谱系的细胞亚群。这些细胞占健康供者CD56(DIM)墨汁总数的19.4%+/-2.8%，表达激活的NKG2D和NKG2E受体，但不表达KIR或NKG2A。尽管CD56dim NKG2-akir(-)NK细胞缺乏“至少一个”自体MHC 1类抑制性受体，但它们不是完全有反应的，而是功能不成熟的细胞，细胞毒性和干扰素-γ产生能力较差。CD56dim和CD56(Bright)KIR-NK细胞在IL-15和基质细胞系的培养下增殖，表达KIR，并具有细胞毒和细胞因子产生的潜能。这些发现对移植后重建的NK细胞的功能有一定的意义，并支持CD56(明亮)细胞先于CD56dim细胞的体内发育模型。
How receptor acquisition correlates with the functional maturation of natural killer (NK) cells is poorly understood. We used quantitative real-time polymerase chain reaction (PCR) assays to compare NKG2 and killer immunoglobulin-like receptor (KIR) gene expression in NK cells from allogeneic transplant recipients and their donors. Marked differences were observed in the NK subsets of recipients who had 8-fold more CD56(bright) cells, diminished KIR expression (except 2DL4), and increased NKG2A. In normal blood not all CD56(dim) cells express KIR, and a novel subpopulation of cells committed to the NK-cell lineage was defined. These cells, which comprise 19.4% +/- 2.8% of the CD56(dim) INK population in healthy donors, express the activating NKG2D and NKG2E receptors but no KIR or NKG2A. Although the CD56dim NKG2-AKIR(-) NK cells lack "at least one" inhibitory receptor for autologous MHC class 1, they are not fully responsive, but rather functionally immature cells with poor cytotoxicity and IFN-gamma production. Upon culture with IL-15 and a stromal cell line, CD56dim and CD56(bright) KIR- NK cells proliferate, express KIR, and develop cytotoxicity and cytokine-producing potential. These findings have implications for the function of NK cells reconstituting after transplantation and support a model for in vivo development in which CD56(bright) cells precede CD56dim cells.