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

Abstract

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.

Critical Role of Qa1b in the Protection of Mature Dendritic Cells from NK Cell‐Mediated Killing

“…However, pathogen infection or TLR ligand stimulation protect DC from NK cell-mediated lysis [23]. It has been suggested that increased expression of classical and non-classical MHC molecules protects the mature DC from NK cell-mediated lysis [16,18]. In the present study, we have investigated the role of Qa1-CD94 ⁄ NKG2A interactions in the protection of mature DC from NK cell-mediated killing both in vitro and in vivo.…”

“…We and others have found that NK cells efficiently lyse immature DC in vitro [16][17][18][19][20][21][22]. However, pathogen infection or TLR ligand stimulation protect DC from NK cell-mediated lysis [23].…”

Multidirectional interactions are bridging human NK cells with plasmacytoid and monocyte-derived dendritic cells during innate immune responses

“…Thus, NK cells would select DCs capable of optimal T-cell priming by eliminating those that failed to undergo maturation during immune responses. 8,10 It has previously been shown that NK cells cocultured with pDCs in the presence of pathogens become activated and acquire For personal use only. on May 9, 2018. by guest www.bloodjournal.org From the ability to kill tumor cells.…”

“…8 Briefly, plastic adherent cells obtained from PBMCs were cultured in RPMI 1640 containing 10% FCS, in the presence of IL-4 and GM-CSF (PeproTech) at final concentrations of 20 ng/mL and 50 ng/mL, respectively. After 6 days of culture, cells were characterized by the CD14 Ϫ CD1a ϩ CD83 Ϫ phenotype corresponding to immature MDDCs (iMDDCs).…”

“…2,3 Several reports have highlighted the importance of the reciprocal interaction between NK cells and DCs during the early stages of innate immune responses. [4][5][6][7][8][9] The NK/DC cross talk can occur within inflamed peripheral tissues and results in a potent DC-induced activation of NK-cell functions, which, in turn, exert a modulatory role on DC activity. Pathogen clearance mediated by innate effector mechanisms is, at least in part, the result of the DC-induced up-regulation of NK-cell cytotoxicity and of the release of antimicrobial cytokines from various cell types recruited at the inflammatory sites.…”