Human natural killer cells: Molecular mechanisms controlling NK cell activation and tumor cell lysis.
Natural killer cells represent a highly specialized lymphoid population with a potent cytolytic activity against virus-infected or tumor cells. Their function is regulated by a series of inhibiting or activating signals. The mechanisms by which NK cells kill susceptible target cells was thought to be elucidated after the discovery of inhibitory receptors specific for MHC-class I molecules: NK cells would kill those target cells that lack MHC-class I molecules. However, the actual scenario revealed more complex with the discovery of activating receptors and their ligands. Thus, in certain pathological conditions, corticosteroid treatment or exposure to TGFbeta, NK cells may under-express activating receptors. In addition, target cells may lack ligands for activating receptors and thus fail to activate NK cells upon cell-to-cell contact. This clearly implies that activation of NK cells and of their potent effector mechanism are under the control of different checkpoints.
Moretta
Lorenzo
L
Istituto Giannina Gaslini, Largo Gerolamo Gaslini 5, 16147 Genova-Quarto, Italy. lorenzomoretta@ospedale-gaslini.ge.it
Bottino
Cristina
C
Pende
Daniela
D
Vitale
Massimo
M
Mingari
Maria Cristina
MC
Moretta
Alessandro
A
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
D015395:Histocompatibility Antigens Class I