The natural killer cell-mediated killing of autologous dendritic cells is confined to a cell subset expressing CD94/NKG2A, but lacking inhibitory killer Ig-like receptors.
The cognate NK-DC interaction in inflamed tissues results in NK cell activation and acquisition of cytotoxicity against immature DC (iDC). This may represent a mechanism of DC selection required for the control of downstream adaptive immune responses. Here we show that killing of monocyte-derived iDC is confined to the NK cell subset that expresses CD94/NKG2A, but not killer Ig-like receptors (KIR). Consistent with these data, the expression of HLA-E (i.e. the cellular ligand of CD94/NKG2A) was down-regulated in iDC. On the other hand, HLA-B and HLA-C down-regulation in iDC was not sufficient to induce cytotoxicity in NK cells expressing KIR3DL1 or KIR2DL. Remarkably, CD94/NKG2A(+)KIR(-) NK cells were heterogeneous in their ability to kill iDC and an inverse correlation existed between their CD94/NKG2A surface density and the magnitude of their cytolytic activity. It is conceivable that the reduced CD94/NKG2A surface density enables these cells to efficiently sense the decrease of HLA-E surface expression in iDC. Finally, most NK cells that lysed iDC did not kill mature DC that express higher amounts of HLA class I molecules (including HLA-E)as compared with iDC. However, a small NK cell subset was capable of killing not only iDC but also mature DC.
Della Chiesa
Mariella
M
Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Italy.
Vitale
Massimo
M
Carlomagno
Simona
S
Ferlazzo
Guido
G
Moretta
Lorenzo
L
Moretta
Alessandro
A
D015703:Antigens, CD / Q000032:analysis*; D002478:Cells, Cultured / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000032:analysis; D015236:HLA-C Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D037181:Lectins, C-Type / Q000032:analysis*; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000032:analysis*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens
D015703:Antigens, CD; D006680:HLA Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C515083:KIR3DL1 protein, human; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human