The small subset of CD56brightCD16- natural killer cells is selectively responsible for both cell proliferation and interferon-gamma production upon interaction with dendritic cells.
The encounter of NK cells with dendritic cells (DC) undergoing maturation may result in the induction of NK cell proliferation. Whether such proliferation involves most NK cells or just a subset has yet to be determined. In the present study we analyzed the nature of such proliferating NK cells by combining carboxyfluorescein succinimidyl ester staining and double-fluorescence cytofluorimetric analysis. Freshly isolated peripheral blood NK cells cultured with LPS and immature DC underwent proliferation; however, proliferating cells were confined to a minor NK cell subset. This subset is characterized by the CD56(bright)CD16(-)NKG2A(+)KIR(-) surface phenotype (KIR, killer Ig-like receptor). This was further confirmed by the fact that, after cell sorting, only the CD56(bright) NK cells were able to proliferate in response to the DC stimulus, whereas the CD56(dull) were not. We also provide evidence that the CD56(bright) subset is the main source of IFN-gamma-producing NK cells, upon interaction with DC. The CD56(bright)CD16(-) NK cells express a panel of surface molecules including CD62L, CCR7 and CXCR3 that may allow their homing either to secondary lymphoid compartments or to inflamed tissues. This implies that, in vivo, the interactions between DC undergoing maturation and CD56(bright) NK cells may occur in different tissues and have different functional implications.
Vitale
Massimo
M
Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Della Chiesa
Mariella
M
Carlomagno
Simona
S
Romagnani
Chiara
C
Thiel
Andreas
A
Moretta
Lorenzo
L
Moretta
Alessandro
A
D019002:CD56 Antigen / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005452:Fluoresceins / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D019707:Receptors, Chemokine / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology*
D019002:CD56 Antigen; D005452:Fluoresceins; D019707:Receptors, Chemokine; D017452:Receptors, IgG; C024098:6-carboxyfluorescein; D007371:Interferon-gamma