Suppression of autoimmune diabetes by soluble galectin-1.
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that targets the beta-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 beta-cells. We demonstrated that in nonobese diabetic (NOD) mice, gal-1 therapy reduces significantly the amount of Th1 cells, augments the number of T cells secreting IL-4 or IL-10 specific for islet cell Ag, and causes peripheral deletion of beta-cell-reactive T cells. Administration of gal-1 prevented the onset of hyperglycemia in NOD mice at early and subclinical 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 beta-cell damage while sparing naive T cells, Th2 lymphocytes, and regulatory T cells in NOD mice. Importantly, gal-1 reversed beta-cell autoimmunity and hyperglycemia in NOD mice with ongoing T1D. Because gal-1 therapy did not cause major side effects or beta-cell toxicity in NOD mice, the use of gal-1 to control beta-cell autoimmunity represents a novel alternative for treatment of subclinical or ongoing T1D.
Perone
Marcelo J
MJ
Thomas E. Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Bertera
Suzanne
S
Shufesky
William J
WJ
Divito
Sherrie J
SJ
Montecalvo
Angela
A
Mathers
Alicia R
AR
Larregina
Adriana T
AT
Pang
Mabel
M
Seth
Nilufer
N
Wucherpfennig
Kai W
KW
Trucco
Massimo
M
Baum
Linda G
LG
Morelli
Adrian E
AE
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D005260:Female; D037483:Galectin 1 / Q000008:administration & dosage / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic
D037483:Galectin 1; D007004:Hypoglycemic Agents