Voss S D, Daley J, Ritz J, Robertson M J
Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
J Immunol. 1998 Feb 15;160(4):1618-26.
Optimal proliferation and expansion of human NK cells require mitogenic cytokines together with cell contact-dependent co-stimulation. Production of mAb that can modulate human NK cell proliferation yielded NKH3, which recognizes the CD94 Ag. NKH3 immunoprecipitates contain approximately 70-kDa heterodimeric complexes consisting of a approximately 25-kDa glycoprotein and approximately 40- to 45-kDa molecules. Analysis by two-dimensional isoelectric focusing/SDS-PAGE suggests that several different 40- to 45-kDa species are present in the CD94 receptor complex in human NK cells. NKH3 reacted with essentially all resting NK cells, although CD94 is expressed at higher levels on the CD56(bright) (i.e., high level of CD56) CD16(dim/neg) (i.e., low level of or absent CD16) subpopulation than on the more abundant CD56(dim)CD16(bright) NK cell subset. Moreover, the Z199 mAb, which appears to recognize NKG2-A species that can form heterodimers with CD94, stained virtually all CD56(bright) NK cells, but only a subset of CD56(dim) NK cells. Ligation of CD94 augmented the proliferation of CD56(bright) NK cells in response to IL-2 or IL-15 by as much as 10-fold. Secretion of IFN-gamma by CD56(bright) NK cells stimulated with IL-2 or IL-15 was also enhanced up to 10-fold after CD94 ligation. CD94 mAb did not consistently costimulate proliferation of or IFN-gamma production by CD56(dim) NK cells cultured with IL-2 or IL-15. In contrast, irradiated K562 cells costimulated proliferation of both CD56(bright) and CD56(dim) NK cells. These results indicate that CD56(bright) and CD56(dim) NK cells can be costimulated through different receptors, which may allow these distinct NK cell subsets to be independently regulated in vivo.
人类自然杀伤细胞（NK细胞）的最佳增殖和扩增需要促有丝分裂细胞因子以及细胞接触依赖性共刺激。能够调节人类NK细胞增殖的单克隆抗体（mAb）产生了NKH3，它识别CD94抗原。NKH3免疫沉淀复合物包含约70 kDa的异二聚体复合物，由一个约25 kDa的糖蛋白和约40至45 kDa的分子组成。二维等电聚焦/SDS-PAGE分析表明，人类NK细胞的CD94受体复合物中存在几种不同的40至45 kDa的蛋白。NKH3与基本上所有静息NK细胞发生反应，尽管CD94在CD56（明亮）（即CD56高水平）CD16（暗淡/阴性）（即CD16低水平或无表达）亚群上的表达水平高于更丰富的CD56（暗淡）CD16（明亮）NK细胞亚群。此外，似乎识别可与CD94形成异二聚体的NKG2-A的Z199单克隆抗体几乎对所有CD56（明亮）NK细胞染色，但仅对一部分CD56（暗淡）NK细胞染色。CD94的连接使CD56（明亮）NK细胞对IL-2或IL-15的增殖反应增强多达10倍。用IL-2或IL-15刺激的CD56（明亮）NK细胞分泌的IFN-γ在CD94连接后也增强了多达10倍。CD94单克隆抗体并不能持续共刺激与IL-2或IL-15一起培养的CD56（暗淡）NK细胞的增殖或IFN-γ产生。相反，经辐照的K562细胞共刺激CD56（明亮）和CD56（暗淡）NK细胞的增殖。这些结果表明，CD56（明亮）和CD56（暗淡）NK细胞可以通过不同的受体进行共刺激，这可能使这些不同的NK细胞亚群在体内受到独立调节。
