Dalbeth Nicola, Gundle Roger, Davies Robert J O, Lee Y C Gary, McMichael Andrew J, Callan Margaret F C
Division of Medicine, Imperial College London, Commonwealth Building, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
J Immunol. 2004 Nov 15;173(10):6418-26. doi: 10.4049/jimmunol.173.10.6418.
Human NK cells may be divided into a CD56(dim) subset and a CD56(bright) subset. In peripheral blood, CD56(dim) NK cells dominate, whereas in lymph nodes, CD56(bright) NK cells are more common. In this study we show that CD56(bright) NK cells accumulate within inflammatory lesions in a wide variety of clinical diseases affecting several different anatomical sites. We demonstrate that when activated by the monokines IL-12, IL-15, and IL-18, these NK cells promote TNF-alpha production by CD14(+) monocytes in a manner that is dependent on cell:cell contact. Conversely, CD14(+) monocytes synergize with monokines to promote IFN-gamma production by these NK cells. Again, this interaction is dependent on cell:cell contact. The experiments show that CD56(bright) NK cells accumulate in inflammatory lesions and, in the appropriate cytokine environment, can engage with CD14(+) monocytes in a reciprocal activatory fashion, thereby amplifying the inflammatory response. Such a positive feedback loop is likely to be important in the pathogenesis of chronic inflammatory conditions such as rheumatoid arthritis.
人类自然杀伤细胞（NK细胞）可分为CD56（dim）亚群和CD56（bright）亚群。在外周血中，CD56（dim）NK细胞占主导，而在淋巴结中，CD56（bright）NK细胞更为常见。在本研究中，我们发现CD56（bright）NK细胞在影响多个不同解剖部位的多种临床疾病的炎症病变中聚集。我们证明，当被单核因子IL-12、IL-15和IL-18激活时，这些NK细胞通过一种依赖于细胞间接触的方式促进CD14（+）单核细胞产生肿瘤坏死因子-α（TNF-α）。相反，CD14（+）单核细胞与单核因子协同作用，促进这些NK细胞产生γ干扰素（IFN-γ）。同样，这种相互作用依赖于细胞间接触。实验表明，CD56（bright）NK细胞在炎症病变中聚集，并且在适当的细胞因子环境中，能够以相互激活的方式与CD14（+）单核细胞相互作用，从而放大炎症反应。这样一个正反馈回路在类风湿关节炎等慢性炎症性疾病的发病机制中可能很重要。
