| First Author | Gebe JA | Year | 2006 |
| Journal | Clin Immunol | Volume | 121 |
| Issue | 3 | Pages | 294-304 |
| PubMed ID | 16979383 | Mgi Jnum | J:115931 |
| Mgi Id | MGI:3692477 | Doi | 10.1016/j.clim.2006.08.002 |
| Citation | Gebe JA, et al. (2006) Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice. Clin Immunol 121(3):294-304 |
| abstractText | We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice and is accompanied by histological evidence of insulitis in the absence of overt diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice is 23% with a mean onset age of 40 weeks and is similar to that reported for RIP-B7/DR0401 mice. A gender preference is observed in that 38% of female mice become diabetic compared to 8% of male mice. |
