TY - JOUR
T1 - Impairment of NK cell function by NKG2D modulation in NOD mice
AU - Ogasawara, Kouetsu
AU - Hamerman, Jessica A.
AU - Hsin, Honor
AU - Chikuma, Shunsuke
AU - Bour-Jordan, Helene
AU - Chen, Taian
AU - Pertel, Thomas
AU - Carnaud, Claude
AU - Bluestone, Jeffrey A.
AU - Lanier, Lewis L.
N1 - Funding Information:
We thank Marina Abramova, Gregory L. Szot, and Paul Wegfahrt for expert assistance with the NOD mice experiments. This work is supported by a UCSF Diabetes Center Pilot & Feasibility Grant, NIH grant CA89189, and JDRFI 4-1999-841. K.O. is supported by Human Frontier Science Program Long-Term Fellowship. J.A.H. is supported by an Irvington Foundation Fellowship. L.L.L. is an American Cancer Society Research Professor.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - 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.
AB - 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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U2 - 10.1016/S1074-7613(02)00505-8
DO - 10.1016/S1074-7613(02)00505-8
M3 - Article
C2 - 12530974
AN - SCOPUS:0037241472
SN - 1074-7613
VL - 18
SP - 41
EP - 51
JO - Immunity
JF - Immunity
IS - 1
ER -
