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Natural killer cells : biology, regulation and clinical importance Volume 4, issue 1, Janvier-Février 1998

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Natural killer cells (NK cells), discovered more than 20 years ago, have long been considered as only capable of exerting a cytotoxic activity, distinct from that exerted by T lymphocytes, as NK cell cytotoxicity is not similarly restricted by MHC class I molecules and occurs in the absence of prior immunisation [1]. However, recent studies have corrected these initial data. Indeed, 1) NK cells can also secrete cytokines, chemokines and hematopoietic growth factors ; 2- NK cell activity (cytotoxicity and lymphokine secretion) is controlled by the recognition MHC class I molecule expressed on target cell surface ; 3) finally, eventhough NK cell natural cytotoxicity occurs in the absence of prior immunisation, ADCC (antibody-dependent cell cytotoxicity) only occurs after induction of antigen-specific immunoglobulin (Ig) synthesis. NK cell activity is constantly regulated by cell surface receptors, which are capable of inhibiting or activating their effector function. This subtle balance between activating and inhibitory signals permits NK cells to preferentially induce the lysis of virus-infected cells as well as tumor cells, and protect normal autologous cells from NK-cell mediated destruction. The analysis of NK cell surface receptors and their analogy to activating receptors expressed on T and B lymphocytes have contributed to our knowledge on the molecular mechanisms involved in NK cell function. This new data as well as the growing interest in NK cell manipulation in anti-tumor and anti-infectious therapies justify a general review on NK cells.