title: Characterization of a novel NKG2D and NKp46 double-mutant mouse reveals subtle variations in the NK cell repertoire.
abstract: The immunoreceptors NKG2D and NKp46 are known for their capacity to activate natural killer (NK) cell cytotoxicity and secretory responses in the contexts of tumors and infections, yet their roles in NK cell education remain unclear. Here, we provide the first characterization of mice deficient for both NKG2D and NKp46 receptors to address the relevance of their concomitant absence during NK cell development and function. Our findings reveal that NK cells develop normally in double-mutant (DKO) mice. Mice lacking NKG2D but not NKp46 showed subtle differences in the percentages of NK cells expressing inhibitory Ly49 receptors and the adhesion molecule DNAM-1. A slightly increased percentage of terminally differentiated NK cells and functional response to in vitro stimuli was observed in some experiments. These alterations were modest and did not affect NK cell function in vivo in response to mouse cytomegalovirus infection. NKp46 deficiency alone, or in combination with NKG2D deficiency, had no effect on frequency or function of NK cells.
authors: Department of Life Sciences, Imperial College London, London, United Kingdom.
authors: Sam
authors: S
authors: Sheppard
authors: Chiara
authors: C
authors: Triulzi
authors: Michele
authors: M
authors: Ardolino
authors: Daniel
authors: D
authors: Serna
authors: Lily
authors: L
authors: Zhang
authors: David H
authors: DH
authors: Raulet
authors: Nadia
authors: N
authors: Guerra
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000172:deficiency / Q000276:immunology*; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000172:deficiency / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse
references: Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8826-31
references: 12060703
references: Blood. 2006 Jan 1;107(1):159-66
references: 16150947
references: Front Immunol. 2012 Oct 05;3:300
references: 23060879
references: Annu Rev Immunol. 2001;19:291-330
references: 11244039
references: Nature. 2005 Aug 4;436(7051):709-13
references: 16079848
references: Sci Signal. 2011 Apr 05;4(167):ra21
references: 21467299
references: Curr Opin Immunol. 1999 Jun;11(3):301-7
references: 10375552
references: Blood. 2009 Mar 12;113(11):2434-41
references: 18974374
references: Science. 1999 Jul 30;285(5428):727-9
references: 10426993
references: Blood. 2011 May 19;117(20):5449-52
references: 21422472
references: Annu Rev Immunol. 2013;31:413-41
references: 23298206
references: Immunogenetics. 1995;41(2-3):148-51
references: 7806288
references: Science. 2002 May 17;296(5571):1323-6
references: 11950999
references: J Immunol. 2006 Feb 1;176(3):1517-24
references: 16424180
references: Immunity. 2009 Aug 21;31(2):270-82
references: 19631564
references: Immunity. 2008 Apr;28(4):571-80
references: 18394936
references: Nat Immunol. 2008 May;9(5):477-80
references: 18425103
references: Science. 2012 Jan 20;335(6066):344-8
references: 22267813
references: J Immunol. 2012 Mar 15;188(6):2509-15
references: 22308311
references: Nat Immunol. 2006 May;7(5):517-23
references: 16565719
references: J Immunol. 2012 Mar 1;188(5):2218-26
references: 22287714
references: Blood. 2012 Jul 19;120(3):592-602
references: 22661698
references: Curr Immunol Rev. 2009 Feb;5(1):22-34
references: 19626129
references: Annu Rev Immunol. 2005;23:225-74
references: 15771571
references: Cell Mol Life Sci. 2011 Nov;68(21):3519-29
references: 21898152
references: PLoS Pathog. 2008 Feb 8;4(2):e30
references: 18266471
references: Circulation. 2011 Dec 20;124(25):2933-43
references: 22104546
references: Immunol Rev. 2001 Jun;181:203-14
references: 11513142
references: Immunity. 1999 Nov;11(5):615-23
references: 10591186
references: J Immunol. 2009 Apr 15;182(8):4557-64
references: 19342629
references: Nat Immunol. 2005 Sep;6(9):928-37
references: 16116470
references: Immunity. 2006 Aug;25(2):331-42
references: 16901727
references: J Exp Med. 2008 Aug 4;205(8):1829-41
references: 18606857
references: Nat Rev Immunol. 2007 Sep;7(9):703-14
references: 17717540
references: J Exp Med. 2003 May 19;197(10):1245-53
references: 12756263
references: Nature. 2001 Feb 22;409(6823):1055-60
references: 11234016
references: Annu Rev Immunol. 2001;19:197-223
references: 11244035
references: J Immunol. 2010 Jul 1;185(1):157-65
references: 20530257
references: Blood. 2009 May 28;113(22):5488-96
references: 19234143
references: Immunity. 2012 Jan 27;36(1):55-67
references: 22261438
references: J Exp Med. 2008 Dec 22;205(13):2965-73
references: 19029380
references: Nat Rev Immunol. 2009 Aug;9(8):568-80
references: 19629084
references: J Virol. 2009 Aug;83(16):8108-21
references: 19515783
references: Nat Immunol. 2002 Jun;3(6):523-8
references: 12006976
references: J Exp Med. 1997 Jun 16;185(12):2079-88
references: 9182679
references: J Exp Med. 2008 Aug 4;205(8):1819-28
references: 18606858
references: Eur J Immunol. 2001 Nov;31(11):3370-9
references: 11745355
references: Cell Mol Life Sci. 2011 Nov;68(21):3495-503
references: 21863375
references: Blood. 2011 Nov 17;118(20):5439-47
references: 21931117
references: Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12445-50
references: 8901601