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

Authors

  • Mariella Della Chiesa,

    1. Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genova, Italy
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    • The first two authors contributed equally to this work.

  • Massimo Vitale,

    1. Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
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  • Simona Carlomagno,

    1. Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genova, Italy
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  • Guido Ferlazzo,

    1. Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
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  • Lorenzo Moretta,

    1. Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genova, Italy
    2. Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Genova, Italy
    3. Istituto Giannina Gaslini, Genova, Italy
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  • Alessandro Moretta

    Corresponding author
    1. Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genova, Italy
    2. Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Genova, Italy
    • Dipartimento di Medicina Sperimentale, Sezione di Istologia, Via G.B. Marsano 10, 16132 Genova, Italy Fax: +39–010–512747
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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.

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