Islet regeneration during the reversal of autoimmune diabetes in NOD mice.
Nonobese diabetic (NOD) mice are a model for type 1 diabetes in humans. Treatment of NOD mice with end-stage disease by injection of donor splenocytes and complete Freund's adjuvant eliminates autoimmunity and permanently restores normoglycemia. The return of endogenous insulin secretion is accompanied by the reappearance of pancreatic beta cells. We now show that live donor male or labeled splenocytes administered to diabetic NOD females contain cells that rapidly differentiate into islet and ductal epithelial cells within the pancreas. Treatment with irradiated splenocytes is also followed by islet regeneration, but at a slower rate. The islets generated in both instances are persistent, functional, and apparent in all NOD hosts with permanent disease reversal.
Kodama
Shohta
S
Immunobiology Laboratory, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Room 3602, Charlestown, MA 02129, USA.
Kühtreiber
Willem
W
Fujimura
Satoshi
S
Dale
Elizabeth A
EA
Faustman
Denise L
DL
D000818:Animals; D015551:Autoimmunity; D001786:Blood Glucose / Q000032:analysis; D002454:Cell Differentiation; D002459:Cell Fusion; D017690:Cell Transplantation; D003131:Combined Modality Therapy; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D005260:Female; D005620:Freund's Adjuvant / Q000627:therapeutic use*; D017404:In Situ Hybridization, Fluorescence; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000473:pathology / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D010183:Pancreatic Ducts / Q000166:cytology; D011003:Ploidies; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012038:Regeneration; D013154:Spleen / Q000166:cytology* / Q000528:radiation effects; D013234:Stem Cells / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin; D005620:Freund's Adjuvant; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1