| First Author | Martinez X | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 3 | Pages | 1677-85 |
| PubMed ID | 16034108 | Mgi Jnum | J:100008 |
| Mgi Id | MGI:3586370 | Doi | 10.4049/jimmunol.175.3.1677 |
| Citation | Martinez X, et al. (2005) CD8+ T Cell Tolerance in Nonobese Diabetic Mice Is Restored by Insulin-Dependent Diabetes Resistance Alleles. J Immunol 175(3):1677-85 |
| abstractText | Although candidate genes controlling autoimmune disease can now be identified, a major challenge that remains is defining the resulting cellular events mediated by each locus. In the current study we have used NOD-InsHA transgenic mice that express the influenza hemagglutinin (HA) as an islet Ag to compare the fate of HA-specific CD8(+) T cells in diabetes susceptible NOD-InsHA mice with that observed in diabetes-resistant congenic mice having protective alleles at insulin-dependent diabetes (Idd) 3, Idd5.1, and Idd5.2 (Idd3/5 strain) or at Idd9.1, Idd9.2, and Idd9.3 (Idd9 strain). We demonstrate that protection from diabetes in each case is correlated with functional tolerance of endogenous islet-specific CD8(+) T cells. However, by following the fate of naive, CFSE-labeled, islet Ag-specific CD8(+) (HA-specific clone-4) or CD4(+) (BDC2.5) T cells, we observed that tolerance is achieved differently in each protected strain. In Idd3/5 mice, tolerance occurs during the initial activation of islet Ag-specific CD8(+) and CD4(+) T cells in the pancreatic lymph nodes where CD25(+) regulatory T cells (Tregs) effectively prevent their accumulation. In contrast, resistance alleles in Idd9 mice do not prevent the accumulation of islet Ag-specific CD8(+) and CD4(+) T cells in the pancreatic lymph nodes, indicating that tolerance occurs at a later checkpoint. These results underscore the variety of ways that autoimmunity can be prevented and identify the elimination of islet-specific CD8(+) T cells as a common indicator of high-level protection. |
