Impairment of NK cell function by NKG2D modulation in NOD mice.
Immunity
; 18(1): 41-51, 2003 Jan.
Article
em En
| MEDLINE
| ID: mdl-12530974
ABSTRACT
Nonobese diabetic (NOD) mice, a model of insulin-dependent diabetes mellitus, have a defect in natural killer (NK) cell-mediated functions. Here we show impairment in an activating receptor, NKG2D, in NOD NK cells. While resting NK cells from C57BL/6 and NOD mice expressed equivalent levels of NKG2D, upon activation NOD NK cells but not C57BL/6 NK cells expressed NKG2D ligands, which resulted in downmodulation of the receptor. NKG2D-dependent cytotoxicity and cytokine production were decreased because of receptor modulation, accounting for the dysfunction. Modulation of NKG2D was mostly dependent on the YxxM motif of DAP10, the NKG2D-associated adaptor that activates phosphoinositide 3 kinase. These results suggest that NK cells may be desensitized by exposure to NKG2D ligands.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Receptores Imunológicos
/
Diabetes Mellitus Tipo 1
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article