Suppression of Autoimmune Diabetes by Soluble Galectin-1 (original) (raw)

Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease that targets the β-cells of the pancreas. We investigated the ability of soluble galectin-1 (gal-1), an endogenous lectin that promotes T-cell apoptosis, to down-regulate the T-cell response that destroys the pancreatic β-cells. We demonstrated that in NOD mice, gal-1-therapy reduces significantly the amount of Th1 cells and augments the number of T-cells secreting IL-4 or IL-10 specific for islet cell-Ag, and causes peripheral deletion of β-cell-reactive T-cells. Administration of gal-1 prevented onset of hyperglycemia in NOD mice at early and sub-clinical stages of T1D. Preventive gal-1-therapy shifted the composition of the insulitis into an infiltrate that did not invade the islets, and that contained a significantly reduced number of Th1 cells and a higher percentage of CD4 + T-cells with content of IL-4, IL-5 or IL-10. The beneficial effects of gal-1 correlated with the ability of the lectin to trigger apoptosis of the T-cell subsets that cause β-cell damage, while sparing naïve T-cells, Th2 lymphocytes and regulatory T-cells in NOD mice. Importantly, gal-1 reversed β-cell autoimmunity in NOD mice with ongoing T1D, with reversal of hyperglycemia. Since gal-1-therapy did not cause major side effects or β-cell toxicity in NOD mice, the use of gal-1 to control β-cell autoimmunity represents a novel alternative for treatment of sub-clinical or ongoing T1D.