The incidence of destructive pancreatic infiltrates and overt diabetes in animal models of insulin-dependent (type I) diabetes mellitus can be greatly reduced by inactivating or eliminating most T lymphocytes early in life. Because of theoretical and practical concerns about inducing long-term pan–T-lymphocyte inactivation for prevention or treatment of type I diabetes in humans, we hoped that more selective suppression of only the diabetogenic T lymphocyte population might be possible. To this end, two groups suggested that diabetogenic subpopulations of T lymphocytes in NOD mice could be identified by the protein sequence of their T-lymphocyte receptors. This assertion was based on experimental elimination of candidate T-lymphocyte subpopulations in two different short-term models of diabetes induction in NOD mice. For these experiments, identification and elimination of T-lymphocyte subsets were accomplished with monoclonal antibodies that bind specifically to the variable region of the β-chain (Vβ) of the T-lymphocyte antigen receptor and divide the T-lymphocyte pool of the NOD mouse into ∼20 Vβ subsets. To test the relationship between the two T-lymphocyte Vβ subsets implicated in these studies and pancreatic β-cell destruction in unmanipulated animals, both T-lymphocyte subpopulations identified were genetically eliminated from NOD-derived mice by introduction of a mutant T-lymphocyte receptor Vβ gene, from which these sequences are genomically deleted. Histological evidence of severe β-cell destruction and overt diabetes was found in mice homozygous for the deleted Vβ gene, indicating that neither Vβ gene segment identified in previous studies is required for diabetogenesis in unmanipulated diabetes-prone mice.
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November 01 1991
Diabetes in NOD Mice Does not Require T Lymphocytes Expressing Vβ8 or Vβ5
Marcia McDuffie
Marcia McDuffie
The Barbara Davis Center for Childhood Diabetes and Department of Pediatrics, University of Colorado Health Sciences Center
Denver, Colorado
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Address correspondence and reprint requests to Dr. Marcia McDuffie, Box B140, 4200 East 9th Avenue, Denver, Colorado 80262.
Diabetes 1991;40(11):1555–1559
Article history
Received:
July 01 1991
Revision Received:
July 26 1991
Accepted:
July 26 1991
PubMed:
1936613
Citation
Marcia McDuffie; Diabetes in NOD Mice Does not Require T Lymphocytes Expressing Vβ8 or Vβ5. Diabetes 1 November 1991; 40 (11): 1555–1559. https://doi.org/10.2337/diab.40.11.1555
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