Ganglioside GM1 Deficiency in Effector T Cells From NOD Mice Induces Resistance to Regulatory T-Cell Suppression

Abstract

GM1 deficiency occurs in NOD Teffs and contributes importantly to failed suppression, which is rectified by increasing Teff GM1. Such elevation also reverses subthreshold Ca(2+) influx via TRPC5 channels, an essential aspect of suppression. Our results also support a critical role for galectin-1 as a GM1 cross-linking counter-receptor that fittingly is upregulated and released by Tregs during activation. These findings suggest a novel mechanism by which pathogenic Teffs evade regulatory suppression, thereby leading to autoimmune β-cell destruction and type 1 diabetes.