title: NKG2D-RAE-1 receptor-ligand variation does not account for the NK cell defect in nonobese diabetic mice.
abstract: NK cells from NOD mice induced with poly(I:C) in vivo exhibit low cytotoxicity against a range of target cells, but the genetic mechanisms controlling this defect are yet to be elucidated. Defects in the expression of NKG2D and its ligands, the RAE-1 molecules, have been hypothesized to contribute to the reduced NK function present in NOD mice. In this study, we show that segregation of the NK-mediated killing phenotype did not correlate with the NOD Raet1 haplotype and that the large alterations in NKG2D expression previously reported on NK cells expanded in vitro were not observed in primary, poly(I:C)-elicited NK cells in vivo. Additional studies indicate a complex genetic control of defective NOD NK cells including genes linked to the MHC and possibly those that are associated with an altered cytokine response to the TLR3-agonist poly(I:C).
authors.affiliation: Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Maier
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Howlett
authors.forename: Kara M
authors.initials: KM
authors.lastname: Rainbow
authors.forename: Jan
authors.initials: J
authors.lastname: Clark
authors.forename: Joanna M M
authors.initials: JM
authors.lastname: Howson
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wicker
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005434:Flow Cytometry; D007369:Interferon Inducers / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics* / Q000276:immunology; D011070:Poly I-C / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007369:Interferon Inducers; C527086:Klrk1 protein, mouse; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011070:Poly I-C