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Immunity. 2004 Jun;20(6):757-67.

NKG2D blockade prevents autoimmune diabetes in NOD mice.

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Department of Microbiology and Immunology and The Cancer Research Institute, HSE 1001, Box 0414, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.


NKG2D is an activating receptor on CD8(+) T cells and NK cells that has been implicated in immunity against tumors and microbial pathogens. Here we show that RAE-1 is present in prediabetic pancreas islets of NOD mice and that autoreactive CD8(+) T cells infiltrating the pancreas express NKG2D. Treatment with a nondepleting anti-NKG2D monoclonal antibody (mAb) during the prediabetic stage completely prevented disease by impairing the expansion and function of autoreactive CD8(+) T cells. These findings demonstrate that NKG2D is essential for disease progression and suggest a new therapeutic target for autoimmune type I diabetes.

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