Department of Microbiology and Immunology and the Cancer Research Institute, University of California-San Francisco, San Francisco, CA 94143, USA.
Blood. 2010 Nov 11;116(19):3865-74. doi: 10.1182/blood-2010-04-282301. Epub 2010 Aug 23.
Natural killer (NK) cells are innate immune lymphocytes that express a heterogeneous repertoire of germline-encoded receptors and undergo a distinct pattern of maturation. CD57 is a marker of terminal differentiation on human CD8(+) T cells. Very few newborn or fetal NK cells express CD57; however, the frequency of CD57-bearing NK cells increases with age. We assessed the transcriptional, phenotypic, and functional differences between CD57(+) and CD57(-) NK cells within the CD56(dim) mature NK subset. CD57(+) NK cells express a repertoire of NK-cell receptors, suggestive of a more mature phenotype, and proliferate less when stimulated with target cells and/or cytokines. By contrast, a higher frequency of CD57(+) NK cells produced interferon-γ and demonstrated more potent lytic activity when these cells were stimulated through the activating receptor CD16; however, they are less responsive to stimulation by interleukin-12 and interleukin-18. Finally, CD57 expression is induced on CD57(-)CD56(dim) NK cells after activation by interleukin-2. A combination of a mature phenotype, a higher cytotoxic capacity, a higher sensitivity to stimulation via CD16, with a decreased responsiveness to cytokines, and a decreased capacity to proliferate suggest that CD57(+) NK cells are highly mature and might be terminally differentiated.
自然杀伤 (NK) 细胞是先天免疫淋巴细胞，表达异质的胚系编码受体谱，并经历独特的成熟模式。CD57 是人 CD8(+)T 细胞终末分化的标志物。很少有新生或胎儿 NK 细胞表达 CD57；然而，携带 CD57 的 NK 细胞的频率随着年龄的增长而增加。我们评估了 CD56(dim)成熟 NK 亚群内 CD57(+)和 CD57(-)NK 细胞之间的转录、表型和功能差异。CD57(+)NK 细胞表达 NK 细胞受体谱，提示表型更成熟，当受到靶细胞和/或细胞因子刺激时增殖较少。相比之下，更高频率的 CD57(+)NK 细胞产生干扰素-γ，当这些细胞通过激活受体 CD16 受到刺激时，表现出更强的裂解活性；然而，它们对白细胞介素-12 和白细胞介素-18 的刺激反应性较低。最后，CD57 表达在 CD57(-)CD56(dim)NK 细胞经白细胞介素-2 激活后被诱导。成熟表型、更高的细胞毒性能力、对 CD16 刺激的更高敏感性、对细胞因子反应性降低以及增殖能力降低的组合表明 CD57(+)NK 细胞高度成熟，可能处于终末分化状态。
