| First Author | André-Schmutz I | Year | 1999 |
| Journal | Eur J Immunol | Volume | 29 |
| Issue | 1 | Pages | 245-55 |
| PubMed ID | 9933106 | Mgi Jnum | J:52915 |
| Mgi Id | MGI:1330657 | Doi | 10.1002/(SICI)1521-4141(199901)29:01<245::AID-IMMU245>3.0.CO;2-O |
| Citation | Andre-Schmutz I, et al. (1999) Cellular and molecular changes accompanying the progression from insulitis to diabetes. Eur J Immunol 29(1):245-55 |
| abstractText | Insulin-dependent diabetes mellitus (IDDM) is not a disease of unbridled destruction. The autoimmune attack on pancreatic beta cells has two distinct stages - insulitis and diabetes - and progression of the former to the latter appears to be highly regulated. Identifying the factors controlling this transition has been difficult because it is a complex process that occurs non-universally and asynchronously. We have overcome these difficulties by coupling a simplified TCR transgenic (tg) model of IDDM and the immunosuppressive drug cyclophosphamide (CY). Young BDC2.5 TCR tg mice show insulitis but not diabetes; CY treatment provoked diabetes in 100% of animals with rapid, highly reproducible kinetics. This allowed a detailed temporal analysis of changes in cellular organization and cytokine gene expression within the lesion. The monokines IL-18, IL-12 and TNF-alpha were pivotal, their induction occurring almost immediately and their coordinate action being required for the onset of aggression. Other cytokines with direct toxicity for beta cells, including IL-1 -beta, IL-6 and IFN-gamma, were subsequently induced; in contrast, there was no cellular or molecular evidence of cell contact-mediated mechanisms of beta cell death. |
