Patients with chronic pancreatitis have islet progenitor cells in their ducts, but reversal of overt diabetes in NOD mice by anti-CD3 shows no evidence for islet regeneration
- Author(s)
- Phillips, JM; O'Reilly, L; Bland, C; Foulis, AK; Cooke, A;
- Details
- Publication Year 2007-03,Volume 56,Issue #3,Page 634-640
- Journal Title
- DIABETES
- Publication Type
- Journal Article
- Abstract
- Monoclonal antibodies to T-cell coreceptors have been shown to tolerise autoreactive T-cells and prevent or even reverse autoimmune pathology. In type I diabetes, there is a loss of insulin-secreting beta-cells, and a cure for type 1 diabetes would require not only tolerance induction but also recovery of the functional beta-cell mass. Although we have previously shown that diabetic mice have increased numbers of ductal progenitors in the pancreas, there is no evidence of any increase of insulin-secreting cells in the ducts. In contrast, in the adult human pancreas of patients with chronic pancreatitis, we can demonstrate, in the ducts, increased numbers of insulin-containing cells, as well as cells containing other endocrine and exocrine markers. There are also significantly increased numbers of cells expressing the homeodomain protein, pancreatic duodenal homeobox-1. Anti-CD3 has been shown to reverse overt diabetes in NOD mice; thus, we have used this model to ask whether monoclonal antibody-mediated inhibition of ongoing beta-cell destruction enables islet regeneration to occur. We find no evidence that such monoclonal antibody therapy results in either regeneration of insulin-secreting beta-cells or of increased proliferation of islet beta-cells.
- Publisher
- AMER DIABETES ASSOC
- Keywords
- BETA-CELLS; NONDEPLETING ANTI-CD4; MONOCLONAL-ANTIBODY; AUTOIMMUNITY; TOLERANCE; COSTIMULATION; INTERLEUKIN-1; DESTRUCTION; MELLITUS; RAT
- Publisher's Version
- https://doi.org/10.2337/db06-0832
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2007-03-01 12:00:00