| First Author | Vence L | Year | 2004 |
| Journal | Diabetes | Volume | 53 |
| Issue | 11 | Pages | 2797-803 |
| PubMed ID | 15504959 | Mgi Jnum | J:108733 |
| Mgi Id | MGI:3624604 | Doi | 10.2337/diabetes.53.11.2797 |
| Citation | Vence L, et al. (2004) Fas deficiency prevents type 1 diabetes by inducing hyporesponsiveness in islet beta-cell-reactive T-cells. Diabetes 53(11):2797-803 |
| abstractText | Type 1 diabetes is an autoimmune disease wherein autoreactive T-cells promote the specific destruction of pancreatic islet beta-cells. Evidence for a crucial role for Fas/FasL interactions in this destruction has been highly controversial because of the pleiotropic effects of Fas deficiency on the lymphoid and other systems. Fas-deficient mice are protected from spontaneous development of diabetes not because Fas has a role in the destruction of beta-cells, but rather because insulitis is abrogated. Fas may somehow be involved in the series of events provoking insulitis; for example, it may play a role in the physiological wave of beta-cell death believed to result in the export of pancreatic antigens to the pancreatic lymph nodes and, thereby, to circulating, naive, diabetogenic T-cells for the first time. To explore the implication of Fas in these events, we crossed the lpr mutation into the BDC2.5 model of type 1 diabetes to make it easier to monitor direct effects on the pathogenic specificity. We demonstrated that BDC2.5/NOD(lpr/lpr) mice have qualitatively and quantitatively less aggressive insulitis than do BDC2.5/NOD mice. In vitro proliferation assays showed that BDC2.5/NOD(lpr/lpr) splenocytes proliferated less vigorously than those from control mice in the presence of islet extracts, which reflects their inability to produce interleukin-2, resulting in weaker pathogenicity. |
