A new study reveals distinctive metabolic changes that precede the development of type 1 diabetes (T1D), tossing a stone into the quiet waters of T1D immunology and genetics. The causes of these metabolic changes and their relationship to autoimmunity and β cell destruction are not yet known, but the identification of a metabolic phenotype linked to susceptibility to type I diabetes may help pave the way to a new era of investigation of T1D causality.

Since the identification of ligands for human and mouse DNAM-1, emerging evidence has suggested that DNAM-1 plays an important role in the T cell– and natural killer (NK) cell–mediated recognition and lysis of tumor cells. However, it remains undetermined whether DNAM-1 is involved in tumor immune surveillance in vivo. We addressed this question by using DNAM-1–deficient mice. DNAM-1–deficient cytotoxic T lymphocyte (CTL) and NK cells showed significantly less cytotoxic activity against DNAM-1 ligand-expressing tumors in vitro than wild-type (WT) cells. The methylcholanthrene (MCA)-induced fibrosarcoma cell line Meth A expressed the DNAM-1 ligand CD155, and DNAM-1–deficient mice showed increased tumor development and mortality after transplantation of Meth A cells. Moreover, the DNAM-1–deficient mice developed significantly more DNAM-1 ligand-expressing fibrosarcoma and papilloma cells in response to the chemical carcinogens MCA and 7,12-dimethylbenz[a]anthracene (DMBA), respectively, than did WT mice. These results indicate that DNAM-1 plays an important role in immune surveillance of tumor development.