CD56bright NK cells are enriched at inflammatory sites and can engage with monocytes in a reciprocal program of activation.
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.
Dalbeth
Nicola
N
Division of Medicine, Imperial College London, Commonwealth Building, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Gundle
Roger
R
Davies
Robert J O
RJ
Lee
Y C Gary
YC
McMichael
Andrew J
AJ
Callan
Margaret F C
MF
D001172:Arthritis, Rheumatoid / Q000276:immunology; D019002:CD56 Antigen / Q000096:biosynthesis*; D002449:Cell Aggregation / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D009928:Organ Specificity / Q000276:immunology
D019002:CD56 Antigen; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D007371:Interferon-gamma