CD56bright NK cells are enriched at inflammatory sites and can engage with monocytes in a reciprocal program of activation
CD56bright NK cells are enriched at inflammatory sites and can engage with monocytes in a reciprocal program of activation
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DOI：
10.4049/jimmunol.173.10.6418
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发表时间：
2004-11-15
影响因子：
4.4
通讯作者：
Callan, MFC
中科院分区：
文献类型：
--
作者：
Dalbeth, N;Gundle, R;Callan, MFC
人类NK细胞可分为CD 56（暗）亚群和CD 56（亮）亚群。在外周血中，CD 56（暗）NK细胞占主导地位，而在淋巴结中，CD 56（亮）NK细胞更常见。在这项研究中，我们表明，CD 56（亮）NK细胞在各种临床疾病的炎症病变内积累。影响了几个不同的解剖部位我们证明，当被单核因子IL-12、IL-15和IL-18激活时，这些NK细胞以依赖于细胞：细胞接触的方式促进CD 14（+）单核细胞产生TNF-α。相反，CD 14（+）单核细胞与单核因子协同作用，促进这些NK细胞产生IFN-γ。同样，这种相互作用依赖于细胞：细胞接触。实验表明，CD 56（亮）NK细胞在炎性病变中积累，在适当的细胞因子环境中，可以以相互激活的方式与CD 14（+）单核细胞结合，从而放大炎症反应。这种正反馈回路可能在慢性炎性疾病如类风湿性关节炎的发病机制中很重要。
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.