NKG2D blockade prevents autoimmune diabetes in NOD mice.
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.
Ogasawara
Kouetsu
K
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.
Hamerman
Jessica A
JA
Ehrlich
Lauren R
LR
Bour-Jordan
Helene
H
Santamaria
Pere
P
Bluestone
Jeffrey A
JA
Lanier
Lewis L
LL
D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D005434:Flow Cytometry; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell
D000906:Antibodies; C527086:Klrk1 protein, mouse; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012333:RNA, Messenger; C491219:Raet1a protein, mouse; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell