Activation of NK cell cytotoxicity

Mark J. Smyth, Erika Cretney, Janice M. Kelly, Jennifer A. Westwood, Shayna E.A. Street, Hideo Yagita, Kazuyoshi Takeda, Serani L.H.Van Dommelen, Mariapia A. Degli-Esposti, Yoshihiro Hayakawa

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369 Citations (Scopus)

Abstract

Natural killer (NK) cells are innate effector lymphocytes necessary for defence against stressed, microbe-infected, or malignant cells. NK cells kill target cells by either of two major mechanisms that require direct contact between NK cells and target cells. In the first pathway, cytoplasmic granule toxins, predominantly a membrane-disrupting protein known as perforin, and a family of structurally related serine proteases (granzymes) with various substrate specificities, are secreted by exocytosis and together induce apoptosis of the target cell. The granule-exocytosis pathway potently activates cell-death mechanisms that operate through the activation of apoptotic cysteine proteases (caspases), but can also cause cell death in the absence of activated caspases. The second pathway involves the engagement of death receptors (e.g. Fas/CD95) on target cells by their cognate ligands (e.g. FasL) on NK cells, resulting in classical caspase-dependent apoptosis. The comparative role of these pathways in the pathophysiology of many diseases is being dissected by analyses of gene-targeted mice that lack these molecules, and humans who have genetic mutations affecting these pathways. We are also now learning that the effector function of NK cells is controlled by interactions involving specific NK cell receptors and their cognate ligands, either on target cells, or other cells of the immune system. This review will discuss the functional importance of NK cell cytotoxicity and the receptor/ligand interactions that control these processes.

Original languageEnglish
Pages (from-to)501-510
Number of pages10
JournalMolecular Immunology
Volume42
Issue number4 SPEC. ISS.
DOIs
Publication statusPublished - 1 Jan 2005
Externally publishedYes

Keywords

  • Apoptosis
  • Effector
  • Receptor
  • Tumor
  • Virus

Cite this

Smyth, M. J., Cretney, E., Kelly, J. M., Westwood, J. A., Street, S. E. A., Yagita, H., Takeda, K., Dommelen, S. L. H. V., Degli-Esposti, M. A., & Hayakawa, Y. (2005). Activation of NK cell cytotoxicity. Molecular Immunology, 42(4 SPEC. ISS.), 501-510. https://doi.org/10.1016/j.molimm.2004.07.034