Suppression of autoimmune diabetes by soluble galectin-1

PERONE, M.J.; BERTERA, S.; SHUFESKY, W.J.; DIVITO, S.J.; MONTECALVO, A.; MATHERS, A.R.; LARREGINA, A. T.; PANG, M.; SETH, N.; WUCHERPFENNIG, K.W.; TRUCCO, M.; BAUM, L.G.; MORELLI, A.E.

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Año: 2009 p. 2641 - 2653

0022-1767

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that targets the
-cells of the pancreas. We investigated the abilityof soluble galectin-1 (gal-1), an endogenous lectin that promotes T cell apoptosis, to down-regulate the T cell response that destroysthe pancreatic
-cells. We demonstrated that in nonobese diabetic (NOD) mice, gal-1 therapy reduces significantly the amount ofTh1 cells, augments the number of T cells secreting IL-4 or IL-10 specific for islet cell Ag, and causes peripheral deletion of
-cell-reactive T cells. Administration of gal-1 prevented the onset of hyperglycemia in NOD mice at early and subclinical stagesof T1D. Preventive gal-1 therapy shifted the composition of the insulitis into an infiltrate that did not invade the islets andthat 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 subsetsthat cause
-cell damage while sparing naive T cells, Th2 lymphocytes, and regulatory T cells in NOD mice. Importantly,gal-1 reversed
-cell autoimmunity and hyperglycemia in NOD mice with ongoing T1D. Because gal-1 therapy did not causemajor side effects or
-cell toxicity in NOD mice, the use of gal-1 to control
-cell autoimmunity represents a novel alternativefor treatment of subclinical or ongoing T1D. The Journal of Immunology, 2009, 182: 2641–2653.