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NKG2D is an activating receptor on NK cells and activated CD8 T cells that has been implicated in tumor immunity, viral immunity and autoimmunity. The ligands of NKG2D are tightly regulated stress-inducible molecules, whose expression is triggered by transformation or infection. In mice, these NKG2D ligands include the retinoic acid early inducible-1 (RAE-1) proteins. However, the mechanisms of transcriptional regulation in RAE-1 genes are poorly understood. We examined what transcription factors regulate RAE-1 expression. We found that RAE-1 delta has six exons and RAE-1 epsilon has seven exons. We isolated genomic DNAs of upstream from exon one which are thought of RAE-1 promoters in RAE-1 delta or RAE-1 epsilon. We found that consensus sequences of several transcription factors are present in RAE promoters. Therefore, these transcription factors may regulate RAE-1 expressions. This work is supported by Grants-in Aid for Science Research from the Ministries of Education, Culture, Sports, Science, and Technology of Japan, Grants-in Aid for Science Research from the Ministriesof Health, Labor, and Welfare of Japan, Human Frontier Science Program CDA, The Mitsubishi Foundation, The Sumitomo Foundation, Takeda Science Foundation and Uehara Memorial Foundation.

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.

Induction of the interferon (IFN)-alpha/beta gene transcription in virus-infected cells is an event central to innate immunity. Mice lacking the transcription factor IRF-3 are more vulnerable to virus infection. In embryonic fibroblasts, virus-induced IFN-alpha/beta gene expression levels are reduced and the spectrum of the IFN-alpha mRNA subspecies altered. Furthermore, cells additionally defective in IRF-7 expression totally fail to induce these genes in response to infections by any of the virus types tested. In these cells, a normal profile of IFN-alpha/beta mRNA induction can be achieved by coexpressing both IRF-3 and IRF-7. These results demonstrate the essential and distinct roles of thetwo factors, which together ensure the transcriptional efficiency and diversity of IFN-alpha/beta genes for the antiviral response.