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What is a natural killer cell?

Nature Immunology volume 3, pages 6–8 (2002)Cite this article

Natural killer cells have been arbitrarily defined using a number of different phenotypic and functional criteria. We asked Lorenzo Moretta if we have truly discovered the core identity of this critical player in eliciting immune responses.

Natural killer (NK) cells were originally identified on a functional basis because of their ability to lyse certain tumors in the absence of previous stimulation. They represent a lymphoid population that, in contrast to T or B lymphocytes, does not express clonally distributed receptors for antigen1,2. Under normal conditions, NK cells are mostly confined to peripheral blood, spleen and bone marrow, but can migrate to inflamed tissues in response to different chemoattractants. They appear to play a role in the control of tumor growth in vivo and to prevent the rapid dissemination of metastatic tumors, at least in a murine model3. In addition, NK cells are fundamental in defenses against certain cytopathic viruses, primarily herpesviruses4. Upon activation, NK cells release cytokines and chemokines that induce inflammatory responses, modulate hematopoiesis, control monocyte and granulocyte cell growth and function and influence the type of subsequent adaptive responses1. For many years after their discovery, and despite their relevance in defense mechanisms, major questions concerning the mode of action and exact nature of NK cells remained. However, this has all changed in recent years and we have now a fair idea of the general mechanisms that regulate NK cell activation and function. In particular, the molecular mechanisms that allow NK cells to spare normal cells and kill abnormal target cells have now been clarified.

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Figure 1: Receptors and ligands involved in human NK cell–mediated cytotoxicity.
Figure 2: Donor NK cell–mediated killing of leukemic cells: more than a dream in bone marrow transplantation.

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Acknowledgements

Supported by grants awarded by Associazione Italiana per la Ricerca sul Cancro, Istituto Superiore di Sanità, Consiglio Nazionale delle Ricerche, Progetto Finalizzato Biotecnologie, MURST-CNR 5% CNR Biotechnology program 95/95 and Telethon-Italy (grant number E.0892).

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Authors and Affiliations

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

    Alessandro Moretta & Lorenzo Moretta

  2. Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy

    Cristina Bottino, Maria Cristina Mingari & Roberto Biassoni

  3. Dipartimento di Oncologia, Biologia e Genetica, Università degli Studi di Genova, Genova, Italy

    Maria Cristina Mingari

  4. Istituto Giannina Gaslini, Genova, Italy

    Lorenzo Moretta

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  1. Alessandro Moretta
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  2. Cristina Bottino
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  3. Maria Cristina Mingari
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  4. Roberto Biassoni
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  5. Lorenzo Moretta
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Corresponding author

Correspondence to Lorenzo Moretta.

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Moretta, A., Bottino, C., Mingari, M. et al. What is a natural killer cell?. Nat Immunol 3, 6–8 (2002). https://doi.org/10.1038/ni0102-6

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