Impairment of NK Cell Function by NKG2D Modulation in NOD Mice.
Ogasawara, Kouetsu 1; Hamerman, Jessica A. 1; Hsin, Honor 2; Chikuma, Shunsuke 2; Bour-Jordan, Helene 2; Chen, Taian 1; Pertel, Thomas 1; Carnaud, Claude 3; Bluestone, Jeffrey A. 4,2; Lanier, Lewis L. 4,1,*
[Article] Immunity. 18(1):41-51, January 2003.

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Summary: 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.

(C) 2003Elsevier, Inc.