Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Animals
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Antibodies / immunology
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Antibodies / pharmacology
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Antibodies / therapeutic use
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Division
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Diabetes Mellitus, Experimental / drug therapy
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Diabetes Mellitus, Experimental / immunology
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Diabetes Mellitus, Experimental / metabolism
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Diabetes Mellitus, Experimental / prevention & control
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Diabetes Mellitus, Type 1 / drug therapy*
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Diabetes Mellitus, Type 1 / immunology
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Diabetes Mellitus, Type 1 / metabolism*
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Diabetes Mellitus, Type 1 / prevention & control
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Flow Cytometry
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Islets of Langerhans / cytology
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Islets of Langerhans / drug effects
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Islets of Langerhans / metabolism
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Membrane Proteins / genetics
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Mice
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Mice, Inbred NOD
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Mice, SCID
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Mice, Transgenic
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NK Cell Lectin-Like Receptor Subfamily K
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Immunologic / antagonists & inhibitors*
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism*
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Receptors, Natural Killer Cell
Substances
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Antibodies
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Klrk1 protein, mouse
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Membrane Proteins
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NK Cell Lectin-Like Receptor Subfamily K
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RNA, Messenger
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Raet1a protein, mouse
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Receptors, Immunologic
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Receptors, Natural Killer Cell