| First Author | Sévère S | Year | 2007 |
| Journal | Mol Immunol | Volume | 44 |
| Issue | 11 | Pages | 2950-60 |
| PubMed ID | 17336387 | Mgi Jnum | J:119811 |
| Mgi Id | MGI:3703293 | Doi | 10.1016/j.molimm.2007.01.008 |
| Citation | Severe S, et al. (2007) CD8(+) T lymphocytes specific for glutamic acid decarboxylase 90-98 epitope mediate diabetes in NOD(SCID) mouse. Mol Immunol 44(11):2950-60 |
| abstractText | During the past decade, glutamic acid decarboxylase (GAD) has been considered a crucial beta-cell autoantigen involved in type 1 diabetes in the NOD mouse and human. Recently, the etiological role of GAD has remained controversy. In the NOD mouse, some previous studies argued in favor of a regulatory role for GAD-specific CD4(+) T cells, and no diabetogenic CD8(+) T cells specific for GAD have been identified so far, discrediting the importance of GAD in beta-cell injury. Here, we identified, in the NOD model, a relevant GAD CD8(+) T cell epitope (GAD(90-98)) using immunization with a plasmid encoding GAD, a protocol relying on in vivo processing of peptides from the autoantigenic protein. In pancreatic lymph nodes of naive female NOD mice, CD8(+) T lymphocytes recognizing GAD(90-98) peptide were detected during the initial phase of invasive insulitis (between 4 and 8 weeks of age), suggesting an important role for these cells in the first stage of the disease. GAD(90-98) specific CD8(+) lymphocytes lysed efficiently islet cells in vitro and transferred diabetes into NOD(SCID) mice (100%). Finally, diabetes was accelerated greatly in 3-week-old female NOD mice injected i.p. with GAD(90-98), strengthening the role of GAD-specific CTLs in diabetes pathogenesis. |
